ES2537193T3 - Highly porous self-coiled veil materials with hemostatic properties - Google Patents

Abstract

An implantable article comprising continuous melt-formed bioabsorbable filaments and discontinuous melt-formed bioabsorbable filaments intermingled to form a porous web (22), wherein said filaments are self-cohered with one another at multiple points of contact, wherein said filaments comprise at least one semi-crystalline polymeric component covalently bonded or admixed with at least one amorphous polymeric component, wherein the filaments possess partial to complete phase immiscibility of the polymeric components when in a crystalline state; and wherein said porous web has a porosity percentage greater than ninety in the absence of additional components, wherein the porous web is a uniaxially stretched web and wherein the filaments have been eroded through a carding process when at least some of the filaments of the veil are hooked and separated from each other; and a non-bioabsorbable material (24) removably bonded to a population of said melt-formed filaments.

Description

5

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

E06788161

05-19-2015

DESCRIPTION

Highly porous self-coiled veil materials with hemostatic properties

Field of the Invention

The present invention relates to implantable medical materials and devices. More particularly, the present invention relates to implantable medical materials and devices made of bioabsorbable polymeric materials in the form of nonwoven veils of self-cohesive filaments having a high degree of porosity.

Background of the invention

Various bioabsorbable polymeric compounds have been developed for use in medical applications. Materials made of these compounds can be used to construct implantable devices that do not remain permanently in the body of an implant recipient. Bioabsorbable materials are removed from the body of an implant recipient through a physiological process inherent in the implant recipient. These processes may include the simple dissolution of all or part of the bioabsorbable compound, hydrolysis of labile chemical bonds in the bioabsorbable compound, enzymatic action and / or erosion of the material surface. The degradation products of these processes are normally removed from the implant recipient through the action of the lungs, liver and / or kidneys. In the literature it is recognized that "bioresorbable", "resorbable", "bioabsorbable" and "biodegradable" are terms that are often used interchangeably. In this document, the term "bioabsorbable" is preferred.

Bioabsorbable polymeric compounds have been used for many decades in wound closure and reconstruction applications. Sutures are the most notable examples. Molded articles, films, foams, laminates, woven and nonwoven materials have also been produced with bioabsorbable polymeric compounds.

Biologically active compositions have been released releasably with some of these bioabsorbable compounds.

U.S. Pat. No. 6,165,217 (´217), granted to Hayes, discloses a bioabsorbable material in the form of a self-cohesive nonwoven web (Figures 1 and 1A, herein). A self-cohesive nonwoven web material is a spun web of continuous filaments made of at least one semi-crystalline polymer component covalently bonded as a linear block copolymer or mixed with one or more semicrystalline or amorphous polymer components.

Continuous filaments are produced by selecting the spinning conditions that provide adhesiveness to the emerging filaments and allow them to self-cohesion as solid filaments, since the filaments are collected in a cohesive random pile, or veil, on a collection surface. The spun filaments intermingle as they are collected in the form of a porous veil of self-cohesive filaments. Self-cohesive filaments have multiple points of contact with each other within the veil. Self-cohesive filaments are bonded at the contact points without the need for the required addition of supplementary adhesives, binders, adhesive adjuvants (eg, solvents, adhesion resins, softening agents) or post-extrusion fusion processing. The self-cohesive filaments of the nonwoven web of polyglycolide: trimethylene carbonate (PGA: TMC) of the preferred embodiment have a diameter between 20 micrometers and 50 micrometers. According to Hayes, these self-woven nonwoven veils have densities in volume (also called apparent densities) that indicate that the percentage of porosity is in a range of approximately forty (40) and eighty (80). If the potentially semi-crystalline veil is conserved in a thermodynamically unstable (metastable), homogeneous (disordered microfase) amorphous state, of substantially miscible phase of limited crystallinity, the veil is malleable and can easily be shaped or molded into a desired shape. This form that has taken can then be preserved through its conversion into a more orderly, thermodynamically stable semi-crystalline state of at least partially immiscible phase. This irreversible conversion (which lacks complete recasting and reformation of the veil structures formed) from a prolonged amorphous state (i.e., disorderly miscibility state) to an orderly semicrystalline state is usually provided by chain mobility present in the gummy state. existing between the melting temperature and that of the order-disorder transition temperature (Todt), the temperature above which the transition from disorder to order can occur. Alternatively, solvents, lubricants or plasticizers can be used, with or without their combination with heat, to facilitate chain mobility and reorganization of the constituent polymer chains in a more orderly state. The chemical composition of the self-cohesive filaments can be chosen, so that the resulting veil is implantable and bioabsorbable.

Hayes describes the self-woven nonwoven web material as having a varying degree of porosity based on the deposition density of the fibers and any subsequent compression. Hayes also describes the ability of the flat veil in the unstable malleable amorphous state to conform in an almost unlimited series of shapes, whose conformations can be preserved through subsequent crystallization. However, Hayes does not indicate a non-fixed veil of the self-cohesive filaments that can serve as a precursor veil material for further stretching processing to increase the porosity of the veil before annealing, nor does Hayes teach a self-cohesive non-woven veil material that has a significant population of continuous filaments

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

E06788161

05-19-2015

with a transverse diameter less than twenty (20) micrometers. In the absence of further processing of a precursor web material according to the present invention, Hayes self-woven nonwoven web material would not have a greater molecular orientation in the self-cohesive web filaments to provide a birefringence value greater than 0.050.

A self-woven nonwoven web material having a high porosity and a diameter of the small filaments would have a proportionally increased mechanical strength in one or more directions. Despite the increased mechanical strength, such a high-porosity self-woven nonwoven web material would provide more sponginess, softness, fall quality, formability, tissue understandability and hemostasis than a veil material manufactured in accordance with Hayes.

For non-implantable applications, a self-woven non-woven veil having a high degree of porosity could be used to removably attach implantable devices and materials to a release apparatus. The fabrication of combining a population of oriented filaments with an increased internal vacuum volume within which the oriented filament can move would imbue said material with a degree of elasticity or resilience.

In addition to these and other improvements in said web material, a more porous bioabsorbable web material would provide opportunities to combine other components with the web. The components could be placed on the surfaces of the filaments. The components could also be placed inside the empty spaces,

or pores, between the filaments. The components could be bioabsorbable or non-bioabsorbable. The components, in turn, could removably contain useful substances.

Therefore, there is a need for a bioabsorbable and synthetic non-woven self-coherent polymeric web material having a high degree of porosity with greater mechanical strength, fluffiness, softness, fall quality, adaptability and understandability of the fabric.

Summary of the invention

In accordance with one aspect of the invention an implantable article is provided in accordance with the appended claims.

The implantable article comprises self-coherent, non-woven, bioabsorbable and synthetic polymeric veil materials with a high degree of porosity. The highly porous veil materials are mechanically strong and have a high degree of fluffiness, softness, fall quality, adaptability and understandability of the fabric. In some embodiments, the present invention exhibits elastic properties. The invention is suitable for use as an implantable medical device. The invention is also suitable for use in many cases as a hemostatic or thrombogenic agent in an area of hemorrhage or aneurysm formation. In preferred embodiments, the hemostatic web materials of the present invention are combined with additional materials to form compounds. Additional materials may be bioabsorbable and / or non-bioabsorbable in their composition.

These properties are imparted to the present invention by stretching, or stretching, of a self-cohesive precursor web material not annealed in at least one direction at a specific speed and drawing ratio under defined conditions. The stretching is preferably followed by heat setting and cooling with complete or partial restriction.

Self-cohesive veil materials have filaments linked together at multiple points of contact (Figures 1 and 1A). During processing, the filaments are fixed to each other through the self-cohesion contact points. As the self-coherent filaments stretch, the filaments lengthen and become smaller in their transverse diameter (Figures 2 -4A and 6-7). As the filaments become thinner, a larger empty space is formed between the filaments (Table 12). The structure as it has been stretched is “fixed” or recoated, with complete or partial restriction, to induce at least partial immiscibility of the phases and subsequent crystallization. The finest and largest void filaments generated within the veil material are responsible for many of the improved features of the present invention.

A convenient metric for quantifying the empty space of a porous web material is the percentage of porosity of the finished web material. The porosity percentage compares the density of an unprocessed starting compound with the density of a finished porous veil material. The nonwoven web materials of stretched self-cohesive filaments of the present invention have a porosity greater than ninety percent (90%). In the present invention, the greater porosity imparted to the veil is defined as the empty space provided within the outer limits of the self-coherent stretched veil, without the inclusion of any added load or other components that can effectively reduce the available porosity.

The present invention may include additional compositions placed on and / or within the polymeric components of the web material. Additional compositions can also be placed in empty spaces, or pores, of the veil material. Thus, the compositions may include useful substances contained in removable form. The preferred compositions for placing in empty spaces and surfaces of the present invention are hydrogel-based materials.

5

10

fifteen

twenty

25

30

35

40

Four. Five

E06788161

05-19-2015

In two additional embodiments, the present invention has a porosity percentage greater than ninety-one and ninety-five in the absence of additional components.

These and other features of the present invention, as well as the invention itself, will be more fully appreciated from the figures and the detailed description of the invention.

Brief description of the figures

Figure 1 is a scanning electron micrograph (SEM) of a self-cohesive veil material of the

prior art Figure 1A is a scanning electron micrograph (SEM) of a self-cohesive veil material of the prior art.

Figure 2 is a scanning electron micrograph (SEM) at 50x of an embodiment of the present invention.

which has stretched in only one direction. Figure 2A is a scanning electron micrograph (SEM) at 100x of an embodiment of the present invention that has been stretched in a single direction and constructed from PGA: TMC 50-50.

Figure 3 is a scanning electron micrograph (SEM) of a self-cohesive veil that has been stretched in

two directions substantially perpendicular to each other. Figure 4 is a scanning electron micrograph (SEM) at 50x of an embodiment of the present invention having a shape herein referred to as fleece.

Figure 4A is a scanning electron micrograph (SEM) of a self-cohesive veil that has been stretched in

all directions out from the center of the material. Figure 5 is a schematic illustration of an apparatus suitable for producing a precursor web material for use in the present invention.

Figure 6 is a graph showing the effect of different drawing relationships on the diameter of the

filaments in the finished veil material of the present invention. Figure 7 is a graph showing the percentage of filaments having a diameter less than twenty (20) micrometers for a given drawing ratio.

Figure 8 is a graph showing the birefringence relationship with the diameter of the filament in a material

of the finished veil of the present invention. Figure 9 is an illustration of a veil material of the present invention having at least one additional material placed on surfaces and in empty spaces of the veil material.

Figure 9A is an illustration of a veil material of the present invention having at least two

additional materials placed on surfaces and in empty spaces of the veil material. Figure 10 is an illustration of a veil material of the present invention attached to a compressing material.

Figure 10A is an illustration of a veil material of the present invention attached to a material that makes

compress and placed on a stapler. Figure 10B is an illustration of a veil material of the present invention attached to a compressing material and placed on a stapler.

Figure 11 is an illustration of a veil material of the present invention in the form of a wrap

anastomotic Figure 12 is an illustration of a veil material of the present invention placed between a second material having openings therein through which the veil material is exposed.

Figure 13 is an illustration of a veil material of the present invention having a tubular shape. Figure 14 is an illustration of a veil material of the present invention having a cylindrical shape. Figure 15 is an illustration of a veil material of the present invention and a non-bioabsorbable material. Figure 15A is an illustration of a veil material of the present invention and a base material.

bioabsorbable

5

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

E06788161

05-19-2015

Figure 15B is an illustration of a veil material of the present invention and a non-bioabsorbable base material.

Figure 16 is an illustration of a veil material of the present invention in a tubular form with at least one structural element included therein.

Figure 17 is an illustration of a veil material of the present invention in a tubular form that has the ability to change the dimension radially and longitudinally.

Figure 18 is an illustration of a whole blood clotting time test.

Figure 19 is a photograph of a veil material of the present invention having a very high degree of porosity.

Figure 19A is a photograph of a veil material of the present invention having a very high porosity degree and a metal band attached thereto.

Figure 19B is a photograph of a veil material of the present invention having a very high porosity degree with multiple metal bands attached thereto.

Figure 20 is an illustration of the veil material of Figure 19 placed inside the release device.

Figure 21 is an illustration of a composite material of the present invention having a highly porous self-coiled web material stretched over a non-bioabsorbable material.

Figure 21A is an illustration of a composite material of the present invention having a highly porous self-cohesive web material with a bioactive species contained therein removably layered on a non-bioabsorbable material.

Figure 21B is an illustration of a composite material of the present invention having two or more layers of a highly porous stretched self-cohesive web material placed on a non-bioabsorbable base material.

Figure 21C is an illustration of a composite material of the present invention having two or more layers of a highly porous stretched self-coherent web material placed on a bioabsorbable base material.

Figure 21D is an illustration of a composite material of the present invention having a very highly porous self-coiled web material with a population of continuous and discontinuous filaments therein placed on a non-bioabsorbable base material.

Figure 21E is an illustration of a composite material of the present invention that has a very highly porous stretched self-coiled web material having a population of continuous and discontinuous filaments therein placed on a bioabsorbable base material.

Figure 22 is an illustration of a composite material of the present invention having a cell-impermeable barrier material on two opposite sides of a distensible substrate material.

Detailed description of the invention

The present invention relates to nonwoven, self-cohesive, bioabsorbable and synthetic polymeric web materials having a high degree of porosity. The high degree of porosity imparts many desirable characteristics to the invention. These characteristics include properties of fluffiness, softness, fall quality, adaptability, tissue comprehensibility and hemostatic and thrombogenic. Many of these highly porous materials exhibit substantial mechanical strength. The highly porous web materials of the present invention can be used as implantable medical devices or components thereof. When implanted, the highly porous bioabsorbable veil materials or components of the present invention are removed from the body of an implant recipient by physiological processes inherent to the implant recipient.

The highly porous web materials of the present invention are manufactured by drawing an uncoated, nonwoven, self-cohesive, precursor web material not stretched in one or more directions, sequentially or simultaneously, followed by annealing of the polymeric constituents of the material of veil stretched with heat and / or suitable solvents. The precursor web material is made of continuous filaments formed from semi-crystalline multicomponent polymer systems that, after reaching a steady state, have some indications of immiscibility of the phases of the constituent polymer components of the system. It is believed that the ability of the precursor web material to initially self-cohesion after solidification from the melt is the result of a comparatively reduced crystallization rate. The reduced crystallization rate retains the substantially homogeneous amorphous non-crystalline phase phase within the solidified inactivated filamentous veil until such time as it can come into physical contact with other portions of the

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

60

E06788161

05-19-2015

Continuous filament held in a similar amorphous state of limited crystallization. As the portions of the continuous filaments contact each other at multiple points in the precursor web material, the filaments are joined together at the contact points in a solidified state without requiring added adhesive binders, adjuvants or post-extrusion fusion processing. Continuous or discontinuous filaments connected in this way are considered "self-cohesive."

It is expected that the mixture and the copolymer systems that exist in a state of complete miscibility of the components in their amorphous phase, whether in a metastable state or in equilibrium state, show a single Tg or Todt that occurs at a temperature that is a function of the composition of the systems and substantially predictable when the Fox equation is used. On the contrary, it is expected that completely immiscible amorphous multiphase systems will show distinct Tg that correlate with the homopolymer analogs for each separate immiscible phase. In a partially miscible system, some crystallizable or other constituents remain miscible within the existing amorphous phase due to reasons such as steric restrictions or segment inclusions. As a result, the respective Tg would move away from that of their non-crystallizing analog homopolymer towards a temperature that reflects the proportion of the constituent existing within the amorphous phase, a value that could be interpreted using the Fox equation.

Similarly, it is expected that non-crystallizing or amorphous inclusions within the crystalline regions of said partially miscible systems, when present at sufficient concentrations, will produce a diluting or colliding effect resulting in a depression of the melting temperature with respect to as expected from a crystallized homopolymer analog. Such partially miscible systems would result in the depression of the observed Tm, while a completely separate phase system would retain a Tm similar to that of the homopolymeric analog.

In the present invention, the self-cohesive precursor veil material can be suspended in a metastable, non-crystalline amorphous and substantially homogeneous mixed phase state that allows the precursor veil material to be stretched in one or more directions, sequentially or simultaneously, to produce elongation and thinning of the self-cohesive filaments. Stretching a precursor web material increases the empty space between the filaments intermingled in the web material. Although Hayes describes materials with a porosity between approximately forty and eighty percent for a self-assembled veil remanufactured according to the teachings of US Pat. No. 6,165,217, the present inventors have discovered that the precursor web material can have empty spaces that add up to ninety percent (90%) of the total volume of the material. This metric is expressed in this document as a percentage of porosity, or simply "porosity." Porosity is determined as described in Example 3, herein. The finished veil materials of the present invention have porosity values greater than ninety percent (90%) (Table 12).

The prolonged amorphous state present in the precursor web material during processing can be achieved through the selection and preferred use of at least partially immiscible phase mixtures or block copolymers combined with a sufficiently rapid rate of cooling that substantially inhibits separation. of complete or partial microbases, as well as subsequent crystallization. At least partially immiscible phase mixtures of polymers or copolymers may be used provided that the polymer mixture possesses sufficient miscibility in fusion to allow extrusion into filaments. The present invention preferably uses block copolymers that can be described as two block, three block or multiple block copolymers having segmented components of at least partially immiscible phase when they are in a thermodynamically stable state. With immiscibility of the phases in the context of the block copolymers it is intended to refer to segmental components that if a part of a mixture of the homopolymers that are correlated, the phase would be expected to separate within the melt.

More particularly, the present invention preferably uses a three-block ABA copolymer system synthesized by a sequential addition ring polymerization and composed of poly (glycolide), also known as PGA, and poly (trimethylene carbonate), also known as TMC, to form a non-woven, self-cohesive, bioabsorbable, stretched and highly porous material; in which A comprises between 40 and 85 percent by weight of the total weight and in which A is composed of recurring glycolide units; and B comprises the weight of the total weight and is made up of recurring units of trimethylene carbonate, said material being bioabsorbable and implantable. The preferred precursor web materials are made of three-block PGA: TMC copolymers having proportions between PGA and TMC of sixty-seven percent (67%) to thirty-three percent (33%) (67:33 -PGA: TMC) and fifty percent (50%) of PGA to fifty percent (50%) of TMC

(50:50 -PGA: TMC). The inherent viscosity of these polymers at 30 ° C in hexafluoroisopropanol (HFIP) can vary from an average of 0.5 dl / g to more than 1.5 dl / g, and for a preferred use it can vary from 1.0 dl / ga 1.2 dl / g. The acceptable melting point for this particular range of copolymer compositions determined by a DSC melting peak may vary from about 170 ° C to 220 ° C. This accumulated thermal exposure of the copolymers over time, whether by extrusion or other processing, needs to be minimized sufficiently to prevent transesterification reactions that can lead to the degradation of the structure of the block copolymers and their correlated crystallinity and immiscibility characteristics. of the phases.

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

E06788161

05-19-2015

Once a self-coherent continuous filament precursor veil material has been prepared as described herein, the veil material is restricted and preheated above its order-disorder transition temperature (Todt) and below its melting temperature (Tm) for a time sufficient to soften the material without inducing significant crystallization. Then, the softened precursor veil material is stretched in one direction (Figures 2, 2A and 4). The precursor veil material is stretched at a specific speed and at a specific relationship between the initial dimension and the final dimension.

In most unxially stretched embodiments (Figure 2 and 2A), the precursor web material is stretched at speeds preferably from ten to fifty percent (10-50%) of the initial precursor web dimensions per second. For a given drawing speed, a precursor web material can be stretched at a ratio between two to one (2: 1) and eleven to one (11: 1). Preferred ratios are four to one (4: 1), five to one (5: 1), six to one (6: 1), seven to one (7: 1), eight to one (8 : 1), nine to one (9: 1) and ten to one (10: 1). After stretching, the precursor web material is subjected to a heating step to anneal the polymeric material to induce partial or complete phase separation and subsequent crystallization. The annealing step can be performed by one of two procedures.

The first annealing procedure requires keeping the veil at maximum stretch under annealing conditions until the veil is almost or completely annealed. Preferred annealing conditions are 110 ° C to 130 ° C for 0.5 to 3 minutes, although temperatures above the order-disorder temperature (Todt) and below the melting temperature (Tm) could be used , with the appropriate time settings.

The second annealing procedure is referred to herein as "partially retained." In the process, the stretched self-cohesive veil material is partially first counted while being restricted to maximum stretching. The annealing step is then completed with the restriction on the stretched veil material reduced or eliminated. Preferred conditions for this procedure are 70 ° C for 0.5 minutes for the first stage (complete restriction) and 120 ° C for 1 to 2 minutes for the final stage (reduced or unrestricted).

Once annealed, the highly porous self-coiled veil material is removed from the processing apparatus and prepared for use as an implantable medical device or component thereof. The advantage of the partially restricted annealing process is that it allows the stretched veil to be retracted, usually from ten to sixty percent, without an increase in fiber diameter or a reduction in porosity (see, for example, Example 9, cited above). forward) which results in a softer veil. This softness is imparted by winding the fibers in the veil as they retract during the final annealing stage.

The highly porous stretched self-coiled veil materials of the present invention can be combined with each other to form layered or laminated materials. Optionally, the materials can be further processed with heat, binders, adhesives and / or solvents to bond one or more individual layers together. Alternatively, portions of one or more of the layers can remain unbound and separated to form a space between the layers.

In addition, a highly porous stretched self-coiled veil material of the present invention is permanently or temporarily combined with other materials to form composite devices (eg, Figures 15 15B and 21-22). The additional material or materials are made of non-bioabsorbable materials.

The bioabsorbable, self-cohesive, highly porous stretched web material (22) of the present invention is laminated (Figures 15A, 15B, 21B and 21 C), and optionally laminated or otherwise bonded to a piece of non-bioabsorbable material (24). These composite materials are particularly suitable for use as a hemostatic device, a dura replacement in cranial surgery or other barrier material. When used for hemostasis, the highly porous stretched self-absorbed bioabsorbable veil material is placed against a bleeding tissue and the bioabsorbable and / or non-bioabsorbable material is pressed to apply pressure uniformly to the veil material at the site of loss of blood to get hemostasis. In a preferred embodiment, a non-bioabsorbable material is removably attached to the bioabsorbable veil material to allow nontraumatic removal of the non-bioabsorbable material from the area that used to bleed hours or days after hemostasis (Figures 21D and 22). This and other embodiments may include a barrier material (· 0) placed on one or more surfaces of the non-bioabsorbable component of a composite material.

A preferred method of bonding the bioabsorbable web material to a non-bioabsorbable substrate material is with an adhesive made of a bioabsorbable composition in solution. In the process, the dissolved adhesive material is applied to a surface of a substrate material and placed in contact with a population of filaments of a bioabsorbable, self-cohesive, veiled material stretched highly porous until the solvent disperses sufficiently to bind the bioabsorbable veil material to the substrate material with the adhesive.

Preferred non-bioabsorbable materials are fluoropolymeric in composition, with porous expanded polytetrafluoroethylene (ePTFE) and / or fluorinated propylene ether (FEP) being most preferred. Other preferred fluoropolymeric materials are in the form of porous foams as disclosed in US Pat. No. 5,429,869, granted to McGregor et al. Other suitable non-bioabsorbable materials include, among others, polyethylene, polyethylene terephthalate, polypropylene, polyamides and carbon compounds.

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

60

E06788161

05-19-2015

The bioactive substances (27) can be removably placed in or on the highly porous stretched self-cohesive web material of the present invention (Figure 21 A).

In other embodiments (Figure 16), the structural elements (39) are combined with a highly porous stretched self-cohesive web material (· 38) to form a composite construction (36). The structural elements may be made of non-bioabsorbable and / or bioabsorbable materials. The structural elements can be placed on one or both sides of the stretched self-cohesive veil material. The structural elements can also be placed inside the veil material.

In some embodiments, the highly porous stretched self-coiled veil materials may be in the form of a roller, cylinder (Figure 14), rope or tube (Figure 13). The tubular shape can be made "elastic" whose diameter can be lengthened and / or increased (Figure 17). These and other shapes can be adapted for use with a specific anatomical structure or surgical procedure. For example, a self-cohesive veil material stretched highly porous in the form of a sheet can be adapted to place around an anastomotic junction and suture or staple in place (Figure 11). In another embodiment (Figure 10), a material that serves as a compress (14) is combined with an "elastic" shape of the present invention (12) to effect a substantially tubular structure (10) adapted to facilitate the temporary placement of the component that It acts as a compress on a stapler cartridge (Figures 10A -10B). Alternatively, the present invention can additionally serve as the compressing component.

The high porosity of the stretched self-coiled veil materials of the present invention is further increased by subjecting the veil material to a procedure that removes filaments even to a greater extent. The procedure can also fracture the continuous filaments of the veiled material stretched into pieces to form discontinuous filaments. These highly porous stretched self-coiled veil materials of the present invention have been shown to have highly thrombogenic properties and easily provide hemostasis when manually applied to bleeding tissue with moderate pressure. In a preferred form, the veil material (49) has the appearance of a "cotton ball" (Figure 19). One or more of these "reversible compressible hemostatic cotton balls" (49) can be combined with a release system (48), such as a catheter) for implantation at a bleeding site or aneurysm formation (Figure 20 ). A sheath may be placed around a compressed mass of highly porous veil material to keep the veil in a compressed configuration during the introduction and placement of the veil material in an internal area of bleeding. Once in place, the sheath is removed from around the veil material and the body of a patient. The compressed veil material is now free to expand, contact and adapt to the hemorrhagic tissue and exert its hemostatic or thrombogenic effects to stop the bleeding. Additional elements, such as metal bands (Figures 19A-B), can be added to the self-coiled veiled material stretched very highly porous as auxiliary elements for visualization or mechanical supports. When used as a component of a medical device, these highly porous, hemostatic or thrombogenic veil materials can provide a seal between the device and the surrounding anatomical structures and tissues.

In a preferred embodiment, one or more layers of highly porous stretched self-cohesive web material of the present invention are bonded to a non-bioabsorbable material to form a compound (Figures 21D -22). When used for hemostasis, the self-absorbed bioabsorbable veil material stretched very highly porous is placed against a bleeding tissue and non-bioabsorbable material and pressed to apply pressure evenly to the veil material at the site of blood loss until Get hemostasis. The non-bioabsorbable material is removably attached to the self-absorbed self-absorbed bioabsorbable web material stretched very highly porous to allow non-traumatic removal of the non-bioabsorbable material from a patient's body hours or days after hemostasis. The non-bioabsorbable material of the compound may have a material placed thereon that serves as a vehicle for the highly porous stretched web material. The non-bioabsorbable material can also serve as a barrier to liquids and / or growth into cells or cell processes (Fig. 22, item 30). Preferred non-bioabsorbable materials are fluoropolymeric in composition, with porous expanded polytetrafluoroethylene (ePTFE) and / or fluorinated propylene ether (FEP) being most preferred. Other preferred fluoropolymeric materials are in the form of porous foams as disclosed in US Pat. No. 5,429,869, granted to McGregor et al. Porous foamy fluoropolymeric materials are preferably made by expanding a dispersion of polytetrafluoroethylene (PTFE) particles with expandable microspheres. The microspheres are mixed in the PTFE dispersion and exposed to heat or other suitable energy source. The microspheres comprise a plastic coating that surrounds an expandable liquid or volatile gaseous fluid. As explained in US Pat. No. 3,615,972 granted to Morehouse et al., Thermoplastic microspheres are adapted to expand dramatically when exposed to heat. These microspheres are monocellular particles that comprise a body of resinous material that encapsulates a volatile fluid. When heated, the resinous material of the thermoplastic microspheres softens and the volatile material expands, which causes the entire microsphere to increase substantially in size. With cooling, the resinous material of the microsphere shell stops flowing and tends to retain its enlarged dimension; The volatile fluid inside the microsphere tends to condense, which reduces the pressure in the microsphere. Typically, the resulting porous foam PTFE material does not require sintering. Other suitable non-bioabsorbable materials include, among others, polyethylene, polyethylene terephthalate, polypropylene, polyamides and carbon compounds.

fifteen

25

35

Four. Five

55

E06788161

05-19-2015

Various chemical components (23) can be combined with the highly highly porous stretched self-coiled veil materials (20) of the present invention (Figure 9). The chemical components can be placed on surfaces of the polymeric material comprising the highly porous web material. Chemical components can also be placed in empty spaces, or pores, of the veil material. The chemical compositions may suitably be viscous chemical compositions, such as a hydrogel material. Biologically active substances (27) can be combined with the additional chemical component (Figure 9A). With hydrogel materials, for example, biologically active substances can be released directly from the hydrogel material or released as the hydrogel material and the underlying veil material are bioabsorbed by the body of an implant recipient. Preferred chemical components are in the form of hydrogel materials.

Suitable hydrogel materials include, but are not limited to, polyvinyl alcohol, polyethylene glycol, polypropylene glycol, dextran, agarose, alginate, carboxymethyl cellulose, hyaluronic acid, polyacrylamide, polyglycidol, polyvinyl alcohol-ethylene), poly (ethylene glycol-co-propylene glycol) ) vinyl acetate-co-vinyl alcohol), poly (tetrafluoroethylene-vinyl co-alcohol), poly (acrylonitrile-co-acrylamide), poly (acrylonitrile-co-acrylic acid-acrylamide), poly (acrylonitrile-acrylic acid-acrylamide), polyacrylic acid, poly-lysine, polyethyleneimine, polyvinylpyrrolidone, polyhydroxyethylmethacrylate, polysulfone, mercaptosilane, aminosilane, hydroxylsilane, polyallylamine, polyaminoethyl methacrylate, poliornitine, polyaminoacrylamide, acryloxyacidimide or polyacryloxyaceros, combination polyacryloximide Suitable solvents for dissolving hydrophilic polymers include, among others, water, alcohols, dioxane, dimethylformamide, tetrahydrofuran and acetonitrile etc.

Optionally, the compositions can be chemically altered after combining with the veil material. These chemical alterations can be chemically reactive groups that interact with polymeric constituents of the web material or with chemically reactive groups on the compositions themselves. These chemical alterations of these compositions can serve as binding sites to chemically bind to other chemical compositions, such as biologically active substances (27). These "bioactive substances" include enzymes, organic catalysts, ribozymes, organometallic, proteins, glycoproteins, peptides, polyamino acids, antibodies, nucleic acids, steroid molecules, antibiotics, antifungals, cytokines, carbohydrates, oleophobic, lipids, extracellular matrix material and / or its individual components, pharmaceutical substances and therapeutic substances. A chemically preferred bioactive substance based is dexamethasone. Cells, such as mammalian cells, reptile cells, amphibian cells, bird cells, insect cells, plant cells, vertebrate cells and non-mammalian marine invertebrates, plant cells, microbial cells, protists, genetically modified cells and organelles , such as mitochondria, are also bioactive substances. In addition, non-cellular biological entities, such as viruses, virenes and prions, are considered bioactive substances.

In applications where sterilization of an embodiment of the present invention is desired or required, it is often preferred to sterilize the invention within a suitable container. The invention can be compressed in some containers more than desired in use. In these embodiments, manipulation of the veil material may be necessary to return the invention to a desired conformation. In some embodiments, the compressed veil material may be returned to a less dense configuration with the application of static electricity. In one embodiment, a storage container is provided for an embodiment of the invention having a material that interacts with the veil material as it is removed from the storage container to generate a static electricity charge on the web material. The static electricity charge urges the filaments of the veil material that repel and move away from each other. As the filaments move away from each other, the veil material returns to its original density. Suitable materials for generating a static electricity charge on the veil materials of the present invention include, among others, triboelectric series materials.

The following examples are included for the purpose of illustration of certain aspects of the present invention.

Examples

Example 1

This example describes the formation of an article of the present invention. Initially an uncoated nonwoven self-coherent polymeric precursor veil was formed. The precursor veil material was slightly heated and subjected to stretching in a single direction, or uniaxial, to increase the porosity of the veil material. The highly porous self-coiled veil material was then subjected to heat fixation.

The precursor web material was formed from a segmented three-block copolymer of 67% poly (glycolide) and 33% poly (trimethylene carbonate) (w / w) (67% PGA: 33% TMC). The copolymer is available in resin form from United States Surgical (Norwalk, Connecticut, USA), a unit of Tyco Healthcare Group LP. This polymer is usually called polyglyconate and has historically been available through the formerly called Davis & Geck (Danbury, Connecticut). Earlier Hayes characterized a typical resin batch of 67% PGA: 33% TMC in US Pat. No. 6,165,217. The process of characterization of the resin material "67:33 -PGA: TMC" is repeated herein.

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

E06788161

05-19-2015

Approximately 25 mg of the copolymer purchased was dissolved in 25 ml of hexafluoroisopropanol (HFIP). The diluted solution produced had an inherent viscosity (VI) of 1.53 dl / g measured with a Cannon-Ubelodde viscometer immersed in a water bath set at 30 ° C (+/- 0.05 ° C).

Approximately 10 mg of the copolymer purchased was placed in a sample vessel for differential scanning calorimetry (DSC) of aluminum, covered and analyzed using a Perkin-Elmer DSC 7 equipped with an Intracooler II refrigeration unit capable of providing cooling to the samples up to temperatures as low as minus forty degrees Celsius (-40 ° C). After preconditioning the sample at 180 ° C for 2 minutes, the sample was cooled to the maximum speed provided by the instrument (parameter -500 ° C / min) and scanned from minus forty degrees Celsius (-40 ° C) to two hundred fifty degrees Celsius (250 ° C) at a scanning speed of 10 ° C / min. After finishing this initial scan, the sample was immediately cooled to the maximum speed provided by the instrument (-500 ° C / min parameter). A similar second scan was performed with the same sample over the same temperature range. After finishing the scan and a thermal maintenance at 250 ° C for 5 minutes, the sample was cooled again to the maximum speed provided by the instrument and a third scan was performed.

Each scan was analyzed for the glass transition temperature (Tg) observed, order transition temperature disorder (Todt), crystallization exotherm and melting endotherm. The results are summarized in Table 1.

TABLE 1

Tg / Todt

Tg / Todt

Peak of exotherm Enthalpy of exotherm Melting peak Enthalpy of fusion

Heat 1

0.2 ° C 0.26 J / g * ° C None Any 213.7 ° C 44.7 J / g

Heat 2

17.0 ° C 0.59 J / g * ° C 113.7 ° C -34.2 J / g 211.4 ° C 41.2 J / g

Heat 3

17.0 ° C 0.51 J / g * ° C 121.4 ° C -35.3 J / g 204.2 ° C 38.5 J / g

To prepare the copolymer resin for processing in a precursor web material, approximately 100 grams of the copolymer was heated overnight under vacuum (<5.33 kPa) between 115 ° C and 135 ° C. The resin was pelletized by milling the copolymer in a granulator equipped with a sieve having a hole of four (4) mm (Rapid Granulator, Model 611-SR, Rockford, Illinois, USA).

A 1.27 cm single screw extruder was obtained (Model RCP-0500, Randcastle Extrusion Systems, Inc., Cedar Grove, New Jersey, USA) with a bundle assembly for bonded fiber spinning (JJ Jenkins , Inc., Matthews, NC, USA). The lower portion of the spun-pair package assembly had a row of seven (7) holes (see, "spinning package" in FIG. 5) consisting of openings in the 0.33 mm diameter mold arranged in a configuration circular 2.06 cm in diameter. The spun-pair assembly was set at a temperature between 250 ° C and 270 ° C. The concrete temperature depended on the inherent viscosity characteristics of the resin.

An adjustable arm that held a Vortec Model 902 TRANSVECTOR® (Vortec Corporation - Cincinnati, Ohio USA) was attached to the spinning package and placed in alignment with the direction of travel of a mesh web collection tape and below the base of the row (FIG. 5). The top of the TRANSVECTOR® inlet was centered below the holes in the mold at an adjusted distance "A" (FIG. 5) of approximately 2.5 to 3.8 cm. The arm was mounted on a mechanical device that caused the TRANSVECTOR® to swing through the fabric collector in the same direction as a moving pickup tape. The arm oscillated between the angles of approximately five (5) degrees from the center at a speed frequency of approximately 0.58 complete sweep cycles (approximately 35 complete cycles per minute). The TRANSVECTOR® was connected to a source of pressurized air of approximately 50 to 55 psi (0.34-0.38 MPa). The pressurized air was at room temperature (20-25 ° C), a temperature higher than the Todt of the polymer. In operation, pressurized air was introduced and accelerated into the throat of the TRANSVECTOR®. The accelerated air stream introduced additional air into the inlet from the multi-hole mold area.

The vacuum dried pelletized copolymer was introduced into the screw extruder (101) and through the row spreader (102) as illustrated in Figure 5. The molten copolymer left the row in the form of seven (7) filaments individual (105). As the air flow entering the TRANSVECTOR® inlet (103) influenced the filaments, the filaments accelerated through the TRANSVECTOR® at a significantly higher speed than without the air drag effect. Then, the accelerated filaments were accumulated on a mesh cloth collection tape (106) located at a distance "107" 66 cm from the output of the TRANSVECTOR® moving at the speed of approximately 20.4 cm / min to form a material veil precursor (108). Increasing the speed of the tape produced a thinner veil material, while slowing the speed of the tape produced a thicker veil material.

The nonwoven precursor web material of self-cohesive filaments, unstretched, uncooked resulting

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

E06788161

05-19-2015

accumulated on the collector tape possessed a relatively consistent sponginess along the direction of the tape movement and possessed approximately 8 centimeters of "usable width". "Usable width" refers to an inner portion of the precursor veil material that has the largest consistency at the macroscopic visual level and fine at the microscopic level. Portions of the precursor veil material outside the "usable width" have filaments that accumulate in such a way that the overall veil decreases in terms of height and density relative to both sides of the center line when observed in line with the direction of tape movement. The area densities reported herein were obtained from representative samples acquired from a region of the veil that has a "usable width".

After more than 10 seconds of cooling to room temperature, the precursor veil was removed from the cloth tape. After inspection, the material was a soft-touch cohesive fibrous web with individual component fibers that did not appear to fray or separate from the veil when subjected to moderate handling. The filaments intermingled and joined at the contact points to form a non-stretched non-stretched self-woven precursor nonwoven web material (ie, minimally crystallized or "not fixed").

Precursor veils produced in this way normally possess inherent viscosity values (VI) and crystallization exothermic peaks similar to those described in Example 2 of US Pat. No. 6,165,217, granted to Hayes. Particularly pertinent portions of the example are reproduced herein as follows.

Inherent viscosity

Approximately 29 mg of the precursor veil described above was dissolved in 25 ml of hexafluoroisopropanol (HFIP) to produce a diluted solution. The solution had an inherent viscosity (VI) of 0.97 dl / g measured using a Canon-Ubbelohde viscometer immersed in a water bath at 30 ° C (+/- 0.05 ° C). Consequently, it was observed that the VI had decreased during processing from the initial value of 1.53 dl / g in the pelletized copolymer to a value of 0.97 dl / g in the precursor veil.

Thermal properties

A sample of the appropriate size was obtained from the precursor veil described above to allow this thermal analysis using a differential scanning calorimeter (DSC) of Perkin Elmer DSC7. The scan was performed at 10 ° C / minute and the temperature of the instrument was moderated with an Intracooler II refrigeration unit. A single scan was performed between minus twenty degrees Celsius (-20 ° C) and 250 ° C with the following results (TABLE 2).

TABLE 2

Tg / Todt

Tg / Todt capacity Peak of exotherm Enthalpy of exotherm Melting peak Enthalpy of fusion

Heat 1

16.32 ° C 0.54 J / g * ° C 88.16 ° C -31.68 J / g 209.70 ° C 45.49 J / g

The order-disorder transition temperature (Todt) reported herein occurs at the point of inflection between the different levels of thermal capacity indicated by a deflection greater than 0.1 joules per gram-degree centigrade (J / g * ° C) at baseline sweep. This Todt is produced at a temperature between the glass transition temperatures (Tg) of the respective homopolymers and is approximated more or less by the Fox equation. In this specific example, the precursor veil sample showed an order-disorder transition at approximately 16 ° C and an exotherm of crystallization that begins at approximately 70 ° C. The complete crystallinity of the sample is considered proportional to the area under the fusion endotherm, quantified by enthalpy in joules / gram (J / g). The general characteristics of a thermal scan of this precursor veil can be seen in FIG. 3 of the '217 patent cited above.

Ensuring that the veil was not exposed to combinations of heat or time that would lead to a substantial reduction in the enthalpy of exotherm of the crystallization of the precursor veil, measured by the aforementioned evaluation with DC system based on power compensation, the ends set of the rectangular segments of the precursor veil were then placed with retention and stretched in a single transverse, or uniaxial, direction (ie, in a direction approximately 90 degrees from the longest length of the precursor veil).

The highly porous stretched self-coiled veil materials of the present invention were made with a transverse stretching / expansion machine equipped with prisoner retaining rings and three electric heating zones. Said machine is also known as an adjustable tensioner or tensioning frame with the ability to expand transversely across the surface of a support metal sheet while moving in a longitudinal direction. Due to the wide capacity of adjustment, numerous suppliers have

10

fifteen

twenty

25

30

35

40

E06788161

05-19-2015

of several machines capable of fulfilling the functions described in this document, one of them is: Monforts, A Textilmaschinen GmbH & Co KG, Moechengladbach, Germany.

This concrete unit was equipped with three (3) sequence set of hot plates measuring 61, 15.2 and 61 cm in length, respectively. The hot plates created heated areas through which the veil material was passed. The leading edge of a 33 cm long transition-stretched region began 27.9 cm from the leading edge of the first heated zone. The initial feed rate was 30.48 cm per minute.

In the initial stretching operation, only the third, or last downstream, of the stretching machine was heated to a temperature of 120 ° C. However, unexpectedly it was discovered that heat from the third zone progressively invaded the adjacent first and second zones in such a way that the precursor veil had warmed before it was stretched. Among other things, this resulted in a progressive improvement of the uniformity of the final highly porous web material. The precursor veil materials were stretched to proportions of 2: 1, 3: 1, 4: 1, 5: 1 and 6: 1. Preferred materials were formed when zone one (1) of the transverse stretching apparatus was set at a temperature of 50 ° C and the precursor web material was stretched at a ratio of 6: 1.

After heat setting the stretched veil at a temperature of about 120 ° C for about a

(1) minute), a highly porous self-cohesive web material of the present invention was formed and allowed to cool to room temperature. It was discovered that each piece of material of the invention was more porous, soft, spongy, understandable and uniform in appearance than a similar self-cohesion nonwoven web without preheating and stretching of the similar veil in an uncooked state.

Additional rectangular sections of the precursor veil materials were stretched to proportions of 8: 1 and 10: 1 using preheated plates set at approximately 50 ° C, 75 ° C, and 125 ° C for each successive heated zone in the stretching apparatus. The first two parameters of the thermal zone provided a reliable "preheating" of the precursor web material. The temperatures, higher than the Todt notified in the '217 patent were sufficient to facilitate the mobility of the copolymer molecules of the precursor web material and provide a more consistent final product. The third heated zone was set at a temperature that at least approximated, and probably exceeded, the temperature of the crystallization exotherm peak (Tcr) described in the ‘217 patent, to anneal, or thermofix, the final web material.

Example 2

In this example, precursor veils produced using the various belt speeds and transverse expansion ratios described in Example 1 were obtained for various veil densities and stretching or stretching ratios. After processing, scanning electron micrographs (SEM) of representative areas of this embodiment of the present invention were generated. Some features of the stretched veil of the present invention and the filaments comprising the veil were quantified as follows.

The transverse diameter of the stretched filaments in each veil material of the present invention was determined by visually examining the SEMs. In each SEM, fifty (50) stretched filaments were chosen at random and the diameter of a cross section of each filament was measured. The cumulative results of these transverse filament diameters are contained in Table 3 and are summarized in Figures 6 and 7. The drawing ratios are expressed as multiples "X." For example, "0X" refers to the unstretched precursor veil material. "4X" refers to a 4: 1 stretch ratio. The tabulated characteristics of the veil were the mean, median, minimum and maximum fiber diameter. In addition, both the number and the percentage of the fifty (50) fibers found to be less than twenty (20) micrometers in the transverse diameter were tabulated.

Table 3 5

Dimensional characteristics of the fibers at various stretching ratios

0X

4X 5X 6X 8X 10X

Half

31.3 19.3 19.2 20.2 19.0 16.0

Median

30.3 18.6 17.6 18.4 18.6 15.0

Network Sample Count

6 2 2 10 2 2

Fiber count (<20 um)

2.8 32.0 34.0 30.5 35.0 40.5

% <20 um

5.7% 64.0% 68.0% 61.0% 70.0% 81.0%

10

fifteen

twenty

25

30

35

40

Four. Five

E06788161

05-19-2015

(continuation)

Dimensional characteristics of the fibers at various stretching ratios

0X

4X 5X 6X 8X 10X

%> 20 um

94.3% 36.0% 32.0% 39.0% 30.0% 19.0%

%> 50 um

1.3% 0.0% 0.0% 0.6% 0.0% 0.0%

Minimum (um)

17.0 7.6 9.6 10.6 9.7 7.3

Maximum (um)

59.4 37.3 38.9 41.9 38.2 39.1

When evaluated with this procedure, it was observed that all the transverse diameters of the fiber in the unstretched uncurved precursor veil (0X) were between seventeen (17) and fifty-nine (59) micrometers. Additionally, more than ninety percent (90%) of the fibers had transverse diameters within the range of twenty (20) and fifty (50) micrometers described in the ‘217 patent cited above. The effect of stretching on the fiber diameter is easily observed from these data. The diameter of the strands of unstretched precursor veils can be reduced when subjected to the stretching process of the present invention. The fiber diameter reduction is easily seen by contrasting the number of fibers in an unstretched veil that has diameters below twenty (20) micrometers (for example, 5.7%), having the number of fibers of the veils stretched diameters less than twenty (20) micrometers. The number of fibers with diameters less than twenty (20) micrometers in a stretched material in the range of the present invention from an average of sixty-four percent (64%) to eighty-one percent (81%). Accordingly, the substantial stretching of a precursor veil produces a significant reduction in the diameter of the fiber in a substantial number of the fibers in the final stretched veil material of the present invention.

Since these veils had been stretched, or stretched, in a single direction, or in a "uniaxial" way, it is remarkable from these same data that twenty (20) to forty (40) percent of the fibers in the veil stretched have diameters greater than 20 micrometers. This mixture of fiber diameters within the stretched veil resulted in an increase in the overall fluffiness of the veil material. The increased fluffiness of the stretched web material correlates with a reduction in both the area density of the veil and the volume density. Volume density is directly related to porosity. The veil materials of the present invention have an increased porosity compared to unstretched veil materials. The increase in porosity and the corresponding reduction in volume density maximize interstitial space within the veil structure. These characteristics increase the opportunity for infiltration of host cells in the veil material. The number and type of cell that inhabits a veil material of the present invention have a direct effect on the bioabsorption of the veil material.

To quantify the actual molecular orientation imparted by the stretching process of the present invention, the birefringence values for various filaments of the veils of the present invention manufactured with different drawing ratios were determined. The birefringence values were obtained using a sliding quartz wedge that allows to possess a polarizing microscope with an optical mesh and a circular rotation state (for example, Nikon Optiphot2-POL). Both the transverse filament diameter and the birefringence values were determined from a sample of filaments actively or passively isolated from the optical influences of the surrounding veil.

Ensuring that no physical distortion artifacts occur during filament isolation, transverse diameter values were determined using consensus optical microscopy and birefringence values. The values were acquired by using a Michel-Levy chart. Such optical equipment is available from several suppliers (for example, Nikon America, Melville, NY). Michel-Levy graphics are available from several vendors (for example, The McCrone Institute (Chicago, IL)).

The birefringence values obtained in this way were analyzed to determine a correlation with the diameter of the filament. It was discovered that the relationship seemed to follow a power function that could be approximated by the equation:

Y = 0.4726X-0.9979

with an R2 value of 0.8211 (see Figure 8). Using this relationship and referring to Figure 8, it was determined that a filament with a transverse diameter of twenty (20) micrometers could be expected to have a birefringence value of approximately 0.024. Therefore, it would be reasonably expected that filaments having transverse diameters less than twenty (20) micrometers had birefringence values greater than 0.025.

10

fifteen

twenty

25

30

35

40

E06788161

05-19-2015

Example 3

As a result of the stretching of the material described in example 1, both the amount of polymeric material per unit area (area density) and the amount of polymeric material per unit volume (volume density) were reduced. A precursor veil (produced at a belt speed of 20.4 cm / minute) was further processed in an oven set at 100 ° C for 25 minutes to fully anneal or "heat set" the veil material.

The uncoated unstretched self-cohesive precursor web material was substantially similar to the web material disclosed in the ‘217 patent. It is determined that a thermofixed version of the precursor web material had an area density of approximately 23 mg / cm2 and a volume density of approximately 0.16 g / cc. Commercially available forms of this type of veil are available at W.L. Gore & Associates, Inc., Flagstaff, AZ, under the trade names GORE Bioabsorbable SeamGuard and GORE Resolut Adapt LT. Each of these unstretched web materials has an area density of 9.7 mg / cm2 and 8.4 mg / cm2, respectively. Each veil material also had a volume density of 0.57 g / cm3 and 0.74 g / cm3, respectively. This corresponded to a percentage of porosity of fifty-six (56) and forty-three (43), respectively.

After uniaxial stretching of a precursor web material of Example 1 at a ratio of 6: 1, it was determined that the material had an area density of approximately 5.3 mg / cm2. This represents a change in area density of approximately seventy-five percent (75%). The unstretched precursor web material of Example 1 had a volume density of 0.16 g / cm 2. In contrast, the unstretched precursor web material of Example 1 had a volume density of 0.083 g / cm2. This represents a reduction in volume density of approximately fifty (50) percent.

It has been reported that the relative polymer density of 67% PGA: 33% TMC (w / w) full density (ρpolymer) is 1.30 grams / cm2 (Mukherjee, D, et al; Evaluation Of A Bioabsorbable PGA: TMC Scaffold For Growth Of Chondrocytes, Abstract # 12, Proceedings of the Society for Biomaterials, May 2005). By comparing this reported polymer density value with the volume density of a web material of the present invention (frame), the percentage of overall porosity in the absence of additional components can be determined by the ratio:

(polymer -frame) polymer X 100

As used herein, the expression "percentage of porosity" or simply "porosity" is defined as the empty space provided within the outer limits of the self-drawn stretched veil, without the inclusion of any load or other added components that may effectively reduce the porosity available.

This evaluation showed that stretching of the precursor veil material of Example 1 increased the porosity percentage of the PGA precursor veil material: eighty-eight percent TMC (88%) in the absence of additional components to approximately ninety-four percent (94%) in the absence of additional components. The percentage of porosity resulting in the absence of additional components of both the precursor and the 6: 1 drawn veil mentioned above is provided in Table 4. Table 4 also provides a summary of the area density, volume density and percentage of porosity of the veil material before and after stretching.

Table 4

Comparison of the physical property of the stretched veil 6: 1

Observation

Precursor veil at 20.4 cm / minute Stretched Veil 6: 1 Exchange Rate (%)

PGA density: TMC = 1.30 g / cm2

Area Density (in mg / cm2)

2. 3 5.3 -77%

Volume Density (g / cm3)

0.158 0.083 -47%

Porosity percentage in the absence of additional components

88% 94% 7%

Example 4

This example describes the generation of tensile-strain stress data for uniaxially stretched web materials (6: 1 stretch ratio) of the present invention. Veil materials were produced according to example 1 with the exception that the belt speed was 0.26 feet / minute (7.9 cm / s).

10

fifteen

twenty

25

30

35

40

E06788161

05-19-2015

Samples of stretched veil materials of the present invention were cut into shapes that have a central strip and enlarged ends, much like the shape of a "dog bone." The dog bone-shaped samples were about half the size described for ASTM D638 Type IV (that is, with a narrow distance of 1 mm and a narrow width of 3 mm). The analysis was performed using an INSTRON® Tensile Tester Model No. 5564 equipped with an extensometer and a 500 Newtons load cell. The software package used to operate the analyzer was Merlin, Version 4.42 (Instron Corporation, Norwood, MA). The caliber length was 15.0 mm. The crosshead speed (XHR) was 250 mm / minute. The data was acquired every 0.1 seconds.

It was found that the percentage (%) of elongation and tensile stress of the stretched veil matrix, measured from the test samples oriented in length to be in line with the direction of the strongest transverse veil was 32, 0% and 60 Mpa, respectively. It was found that the percentage (%) of elongation and tensile stress of the stretched veil matrix, measured from the test samples oriented in their length measured in the downward direction of the weakest veil was 84.7% and 3.4 Mpa, respectively. The tensile stress results for these veils 67:33 -PGA: TMC are summarized in Table 5. For comparative purposes, the mechanical characterization of a thinner veil of 67:33 -PGA: TMC as described in the patent ' 217 is included in Table 5.

The tensile stress of the matrix is used as a means to normalize the tensile stress in the samples in which the thickness measurement can be a problem, said materials of the present invention that possess a high degree of porosity and an easily deformed spongy . By using the area density of the test material and the relative density of its polymer component, the tensile stress approach of the matrix makes a porous sponginess difficult to measure into an equivalent thickness of the full density polymer component. The reduction is proportional to the volume density of the veil divided by the relative density of the polymer component. This equivalent polymer thickness was then used for cross-sectional determinations in the calculation of tensile stress. Said use of the tensile stress of the die has been described in US 3,953,566, of Gore, and US 4,482,516, of Bowman, et al., For use in determining the strength of the materials of expanded porous polytetrafluoroethylene.

To obtain the tensile stress of the matrix, the equivalent thickness of a tensile sample is determined by dividing the area density of the porous structure by the relative density of the polymer component. This value is then substituted in place of the actual thickness of the sample to determine the stress. So:

Equivalent thickness = area density / relative density of the polymer

Provided that the area density and the relative density of the polymer component are known, this value of the equivalent thickness can also be used to convert the tensile stress of a porous sample into a tensile stress value of the matrix. In example 2 of the '217 patent, the maximum tensile stress of the veil material 67:33 -PGA: TMC was reported together with the area density of the test sample and found to be 4.9 MPa and 28.1 mg / mm2, respectively.

Therefore, the tensile stress of the die can be calculated as follows:

image 1

Table 5

na = not acquired

Traction Density

Sample Description

Max force (N) Max effort (MPa) Matrix effort (MPa) Elongation% Area (mg / cm2) Volume g / cm3

Unstretched Precursor Veil

na na na na 44 0.17

U.S. Patent 6,165,217 (Example 2; unspecified orientation)

Not proportioned 4.9 (saline) 22.7 (calculated) Not proportioned 28.1 0.29

Veil sample in transverse stretched transverse direction 6: 1

14.3 3.6 60 32.0 9.6 0.065

5

10

fifteen

twenty

25

30

35

40

E06788161

05-19-2015

(continuation)

Table 5

na = not acquired

Traction Density

Sample Description

Max force (N) Max effort (MPa) Matrix effort (MPa) Elongation% Area (mg / cm2) Volume g / cm3

Veil sample in transverse stretched downward direction 6: 1

1.0 0.34 3.4 84.7 11.5 0.078

As can be seen in the light of the data, it was discovered that the veil material of the present invention was highly anisotropic and possessed reduced resistance and significant elongation in the "downward veil" direction. On the contrary, the resistance was the highest in the direction of stretching and it was found that the tensile stress of the veil matrix in the transverse direction was significantly higher than that of the completely crystallized unstretched veil material described in the patent ' 217 This result provided evidence of the increased molecular orientation of the PGA block copolymers: TMC.

Example 5

This example describes the formation of an article of the present invention using a three-block ABA copolymer of PGA: TMC having a ratio of poly (glycolide) and poly (trimethylene carbonate) (weight / weight) of 50:50.

The synthesis of a typical resin batch of 50% PGA: 50% TMC has been previously described in the ‘217 patent and is repeated herein as follows.

A 4CV Helicone Mixer mixer (Design Integrated Technologies, Warrenton, Va., USA) located in a Class 10,000 clean room and connected to a Sterling brand hot oil system (Model # S9016, Sterling, Inc., Milwaukee , Wis., USA) capable of maintaining temperatures up to 230 ° C was previously cleaned to remove any polymeric or other residue and then dried completely in the air for 2 hours before rejoining the mixing bowl. Then, the dry mixer was preheated to 140 ° C, followed by a purge and then an anhydrous nitrogen blanket was placed at minimum flow during the course of the experiment. An aluminum foil package containing 740.7 grams of trimethylene carbonate was opened and the contents were introduced, followed by mixing with a speed parameter of "6.5." After 10 minutes the stirring was stopped and then 2.73 grams of a combination of 0.228 grams of SnCl2 • 2H2O catalyst and 15.71 grams of diethylene glycol initiator were added directly into the molten TMC. It was recommended to mix and, after 10 minutes, the temperature rose to 160 ° C, which was then followed by an increase to 180 ° C after 30 minutes. After an additional 30 minutes, 75 grams of glycolide monomer was added, followed by an increase in temperature to 200 ° C. After 15 minutes, 675 grams of glycolide was added and the set temperature was immediately changed to 220 ° C. After 40 minutes, the polymerized product was discharged at 220 ° C on a clean release surface, where it solidified as it cooled to room temperature. The light brown polymer thus obtained was then packed in a pyrogen-free plastic bag and then mechanically granulated through a 4.0 mm sieve before further analysis and processing.

In patent ‘217 Hayes further reported that the inherent viscosity (VI) of this batch of 50% PGA resin: 50% concrete TMC was 0.99 dl / g.

Then, a three-block copolymer of 50% PGA: 50% TMC synthesized as described was granulated as described in example 1 and then dried under vacuum for at least 15 hours at 120 ° C to 130 ° C. Approximately 250 grams of ground polymer were introduced into the extruder described in example 1 and heated to a mold temperature of about 230 ° C to 250 ° C. A random continuous precursor veil material, of a width of approximately 5.08 cm, was acquired at a belt speed of approximately 20.4 cm / min. The precursor veil material was morphologically similar to the precursor veil material of 67:33 -PGA: TMC not stretched described in example 1. The individual filaments formed cohesive bonds at the contact points to form a self-cohesive veil. The filament diameter for veil materials produced by this process varied from twenty-five (25) micrometers to forty (40) micrometers. As indicated in the ’217 patent, these veil materials normally have inherent viscosity values of 0.9 dl / g. Typical DSC values for these veil materials are listed in Table 6.

5

10

fifteen

twenty

25

30

35

40

Four. Five

E06788161

05-19-2015

Table 6

Typical DSC values for the PGA precursor veil: TMC (50:50) without setting

Tg / Todt

Tg / Todt capacity Peak of exotherm Enthalpy of exotherm Melting peak Enthalpy of fusion

Heat 1

5 ° C 0.5 J / g * ° C 110 ° C -33 J / g 203 ° C 37 J / g

Stretching of the uncoated nonwoven self-cohesive precursor web material was performed with the same equipment and uniaxial drawing speed as described in Example 1 for the 67:33-PGA three-block self-cohesive precursor web material. : TMC. Precautions were taken so that the unstretched precursor veil was not exposed to combinations of heat or time that led to a substantial reduction in the enthalpy of exotherm of crystallization of the veil before stretching.

In addition to the uniaxial stretching ratios described in example 1, additional uniaxial stretching ratios of 7: 1 to 10: 1 were performed. The oven temperature for zone one (1) was set at forty degrees Celsius (40 ° C) and zone three (3) was set at eighty-five degrees Celsius (85 ° C). Thermofixation of the stretched veil was achieved after approximately one (1) minute in zone three (3) at eighty-five degrees Celsius (85 ° C).

For the veils of the present invention manufactured with a three-block copolymer starting material of

50:50 PGA: TMC, uniaxial stretched veils from 7: 1 to 10: 1 produced veils with the greatest smoothness and uniform appearance.

Example 6

This example describes the formation of an article of the present invention using multiple layers of precursor web material and stretching the stratified material sequentially in perpendicular directions.

A starting material was obtained by layering nine sheets of unstretched unstretched precursor web material manufactured according to Example 1. Each of the nine precursor sheets was produced at a belt speed of 1.58 feet / minute (48 cm / min). Each precursor sheet was found to have an area density of approximately 9.0 mg / cm 2 and a volume density of approximately 0.27 g / cc. Accordingly, one would expect that nine layers of the precursor sheet had an area density of approximately 81 mg / cm2 and a volume density of approximately 0.27 g / cc.

The nine sheets of unstretched unstretched precursor veil were initially oriented so that their width was, in general, in the same "machine direction" using the moving belt to capture the veil as it was formed. The similarly oriented stratified sheets were stretched transversely (i.e., in a direction approximately 90 degrees from the direction of the initial orientation of the uncooked veil) in an oven with each of the three heated zones set at room temperature, 50 ° C and 120 ° C, respectively. The stretching ratio was 6: 1 and the drawing speed was one foot per minute (30.5 cm / min).

The result was an article of the present invention having an area density of 18 mg / cm2. This represents a reduction of almost seventy-six (76) percent of the area density with respect to the precursor veil material. The article had a volume density of 0.11 g / cc. This represents a reduction of almost sixty

(60) percent of the volume density with respect to the precursor web material (0.27 g / cc). The porosity percentage of this veil material was seventy-nine (79).

The percent elongation of the precursor veil and the tensile stress of the matrix of the finished laminated web material was measured in the measured transverse web direction and found to be sixty-four percent (64%) and 48 MPa, respectively. . It was found that the percent elongation and tensile stress of the matrix of the finished laminated web material of the present invention, as measured in the downward direction of the weakest web, was one hundred thirty-three percent 133%) and 5.2 MPa, respectively. These values are greater than those observed with the uniaxially distended single-layer veil of Example 1. The tensile stress of the die in the transverse direction of the veil was also greater than the values of 22.7 MPa reported in the '217 patent. .

The stratified veil material of this example possessed greater smoothness and uniform appearance compared to a non-stretched self-cohesive nonwoven laminated veil material.

Example 7

This example describes materials produced from a first longitudinal veil stretching procedure, followed by a subsequent transverse stretching procedure of the same veil. This veil material is called in

10

fifteen

twenty

25

30

35

E06788161

05-19-2015

this document "longitudinal-transverse stretched veil". Uncoated unstretched self-cohesive precursor web material was prepared according to example 1 and processed as follows to form a material of the present invention. The precursor veil material had an area density of approximately 45 mg / cm2.

When evaluated using DSC parameters as described in Example 1, the thermal characteristics of both the 67:33-PGA: TMC resin used and the resulting uncoated precursor veil were those summarized in the Table

7.

Table 7

DSC values for the 67:33 PGA precursor veil: TMC not fixed

1 sweep

Tg / Todt Tg / Todt capacity Peak of exotherm Enthalpy of exotherm Melting peak Enthalpy of fusion

Resin

13.5 ° C 0.33 J / g * ° C none none 193 ° C 40.5 J / g

Net

18.4 ° C 0.57 J / g * ° C 82.9 ° C -30.1 J / g 196 ° C 39.5 J / g

In this example, five (5) varieties of the stretched web material of the present invention were produced based primarily on the drawing ratio. Using a longitudinal stretching machine capable of stretching the precursor veil of suitable length through the surface of a support metal sheet heated in three zones while moving in a longitudinal direction between different pick-up rollers and adjusted speed, each material of unstretched unstretched precursor veil was first stretched longitudinally at a ratio of 1.5: 1 at a temperature of twenty degrees Celsius (20 ° C) in a direction substantially equal to the direction of the collecting belt used for recovery of the non-precursor veil stretched. This longitudinal direction (for example, the x-axis direction) is referred to herein as the "downward veil" (DW) address.

The longitudinally stretched uncoated self-coiled veil material was then transferred to the hot plate transverse stretching machine described in Example 1. Each of these materials stretched down the veil was then stretched a second time in a "transverse direction" (y axis) perpendicular to the direction of the first longitudinal stretching procedure. This stretched "in transverse direction" is referred to herein as "transverse in the veil" (CW). The first sample (called "1B") was stretched transverse in the veil at a ratio of 2: 1. The following sample ("2A") was stretched in the transverse direction in the veil at a ratio of 3: 1. Each remaining sample (2B, 2C and 2D) was stretched across the veil at a ratio of 3.5: 1, 4: 1 and 4.5: 1, respectively. The heated zones in the first and third furnace were set at fifty degrees Celsius (50 ° C) and at one hundred and twenty degrees Celsius (120 ° C), respectively. The temperature in zone three was sufficient to completely heat set the final stretched web material of the present invention. The resulting material was a fully annealed veil, as evidenced by the thermal characteristics shown in Table 8 that showed a substantial extension capacity in DW.

Table 8

DSC values for 67% PGA veil: 33% longitudinal-transversal TMC

1 sweep

Tg / Todt Tg / Todt capacity Peak of exotherm Enthalpy of exotherm Melting peak Enthalpy of fusion

1 B

11.8 ° C 0.39 J / g * ° C none any 193 ° C 38.6 J / g

2A

11.4 ° C 0.35 J / g * ° C none any 192 ° C 38.9 J / g

2B

11.6 ° C 0.33 J / g * ° C none any 194 ° C 41.0 J / g

2 C

11.1 ° C 0.30 J / g * ° C none any 192 ° C 38.8 J / g

2D

11.3 ° C 0.32 J / g * ° C none any 192 ° C 38.2 J / g

The physical and tensile-strain properties of the longitudinal stretched (1.5: 1) - transverse ((4.5: 1) (2D) veil, together with a completely fixed precursor veil, are summarized in Table 9.

5

10

fifteen

twenty

25

30

35

E06788161

05-19-2015

Table 9 Physical and mechanical properties of the 67:33 PGA veil: longitudinal-transversal TMC

Traction

Density

Sample Description

Max force (N) Max effort (MPa) Matrix effort (MPa) Area (mg / cm2) Volume g / cm3

Unstretched Precursor Veil

9.0 3.6 16.9 22.5 0.28

Displays in the downward direction on the 2D - DW veil (3: 2 DW by 5: 1 CW)

1.3 2.3 10.3 5.2

Veil in the transverse direction of the 2D veil - CW (3: 2 DW by 5: 1 CW)

4.8 5.0 23.1 8.4

Example 8 (comparative)

This example describes the formation of two stretched self-coiled veil materials. Veil materials were simultaneously stretched biaxially in two directions (x axis and y axis) during processing.

An unstretched precursor web material was manufactured according to example 1. The TRANSVECTOR® apparatus was set at a row angle of 8.5 degrees and a scanning speed of approximately 0.46 full cycles per second. The resulting unstretched uncurved precursor web material had a "usable width" of 12.7 cm to 15.2 cm with a veil density of forty (40) to fifty (50) mg / cm 2 produced at a rate of tape of approximately 8 cm / min. The unstretched uncurved precursor veil material was not exposed to temporary combinations of heat or time that would lead to a substantial reduction in the enthalpy of crystallization exotherm.

A pantography was used to biaxially stretch the uncooked precursor veil material to form a first biaxially stretched veil material. A pantograph is a machine capable of stretching the precursor veil material biaxially or uniaxially over a range of speeds and temperatures (for example, from 50 ° C to 300 ° C). The pantograph used in this example was able to stretch a piece of the precursor veil material from a square piece of 10 centimeters by 10 centimeters (10 cm x 10 cm) to a piece of 63.5 centimeters by 63.5 centimeters (63, 5 cm x 63.5). This represented a draw ratio of 6.1: 1 on the x and y axes. To retain the precursor veil material while stretching, the last centimeter of each pantograph arm was equipped with a pin array. There were a total of thirty-two (32) arms on the pantograph, seven on each side plus one in each corner. The pantograph was also equipped with hinge plates, which allowed temperature control of the precursor veil material during processing.

The first biaxially stretched veil material was manufactured by fixing a 12.7 cm square piece of unstretched unstretched precursor veil material (45 mg / cm2) on the cpm pantograph retention frame an initial parameter of ten centimeters by ten centimeters (10 cm x 10 cm). The hinge plates were set at fifty degrees Celsius (50 ° C) and placed on the uncooked veil for two minutes to preheat the precursor veil material more than the Todt of the polymer before stretching. The preheated precursor web material was sequentially stretched at a ratio of 3.6: 1 along the x-axis (descending on the veil) and a 6.0: 1 ratio along the y-axis (transverse), both at a rate of 20 percent per second (20% / s). At the end of the stretching process, the plates were retracted from the biaxially stretched veil material.

A retention frame, thirty-five (30.5) centimeters long and twenty (20) centimeters wide, was inserted into the biaxially stretched veil material of the present invention to hold a portion thereof after removing it from the pantograph pliers. The biaxially stretched veil material was heat set by holding it in the twenty (20)) centimeter by thirty with five (30.5) centimeters frame in an oven set at one hundred and twenty degrees Celsius (120 ° C) for approximately three (3 ) minutes. The first biaxially resulting stretched veil material was removed from the retention frame and the non-retained portion was trimmed.

The first biaxially stretched veil material was analyzed to determine the weight and thickness of the area. From these measurements volume density and porosity were calculated, as indicated in example 3. The weight of the area was measured as described in example 1. The thickness was measured according to the procedure of example 1, except from

10

fifteen

twenty

25

30

35

40

Four. Five

E06788161

05-19-2015

that a glass slide, 25 mm x 25 mm x 1 mm thick, was placed on top of the veil in order to clearly distinguish the top surface of the veil in the optical comparator. The weight of the area was 2.61 mg / cm2, which represents a reduction of approximately ninety-four percent (94%) of the weight of the area of the uncooked precursor veil material. The thickness was 0.44 mm. These values give a volume density of 0.059 g / cm3 and a percentage of porosity of ninety-five (95). This value of the percentage of porosity is twice as high in the void-solids ratio (volume of empty spaces / volume of solids) than the highest porosity disclosed in the ‘217 patent.

A second biaxially stretched web material was manufactured as described above, with the exception of modifications in various process parameter values. For this second stretched veil material, the preheat temperature was set at 70 ° C and the uncooked veil was preheated for approximately 30 seconds. The veil was stretched simultaneously at a ratio of 3.6: 1 along the x-axis and a ratio of 6.0: 1 along the axis and at the same stretching rate of thirty percent per second (30% / se ). The second biaxially stretched veil material was clamped and heat set in a retaining frame in an oven as described above for the first stretched veil material.

The properties of the second biaxially stretched veil material were measured as described for the first stretched veil material. The weight of the area was 3.37 mg / cm2 and the thickness was 0.94 mm. This gave a volume density and a porosity value of 0.036 g / cm3 and 97%, respectively. The ratio between voids and solids of the second biaxially stretched web material is approximately 50% greater than that of the first biaxially drawn web material and about 3 times greater than that disclosed in the ‘217 patent.

Example 9 (comparative)

This example describes the formation of a stretched veil material of the present invention. The stretched veil material has a greater fluffiness and smoothness and substantially retakes its original shape when the applied deformation force is eliminated.

A biaxially stretched veil material was manufactured in accordance with example 8 except that a retention frame was not used to hold the veil material while heat setting in the oven. Instead, the biaxially stretched veil material was freely suspended in the oven from a rack. It was observed that the biaxially stretched veil material contracted when removed from the pantograph. Biaxially stretched veil material contracted more in the oven. The area of the completely stretched veil material was reduced by approximately fifty percent 50%) with this process.

The resulting biaxially stretched and contracted veil material, the veil material was thicker, softer, more spongy and more flexible than the similarly produced stretched veil material of Example 8. In addition, this biaxially stretched veil material and contracted it resumed its original form when the applied deformation force was removed. Resilience property was found in all portions of the biaxially stretched and contracted veil material. Microscopic inspection (50X) of the biaxially stretched and resilient contracted web material revealed highly curved self-cohesive filaments of the material oriented in all directions, including the z axis (i.e., perpendicular to the planar axes x and y). The diameter of these "z-oriented fibers" was similar to that of the "x-axis" and "y-axis" fibers. The bioabsorbable, self-cohesive, biaxially stretched and contracted, resilient, highly porous polymeric web material of the present invention possessed physical and handling characteristics similar to textile materials commonly referred to as "fleece."

The properties of the biaxially drawn and contracted fleece veil material were determined according to the procedures described in example 9 and compared with the second biaxially stretched veil of example 8 in the following table 10:

TABLE 10

Property

Example 9 Example 8

Area weight (mg / cm2) Thickness (mm) Volume density (g / cm3) Porosity (%) in the absence of additional components Empty / solid space ratio

5.13 2.11 0.024 98 49 3.37 0.94 0.036 97 32

Figure 4 is a scanning electron micrograph (SEM) showing the filaments of these materials oriented in multiple directions after the stretching process. With an increase of ten (10X), a series of

20 10

fifteen

twenty

25

30

35

40

E06788161

05-19-2015

filaments appeared oriented in a perpendicular direction (z axis) to the other filaments oriented along the x and y axes of the material. On visual inspection, the thickest articles of the present invention had a fleece-like appearance that has a deep stack, a high degree of sponginess and a very high porosity percentage.

Example 10 (comparative)

This example describes the formation of articles of the present invention by stretching the precursor web material radially in all directions simultaneously. The precursor veil materials with one or more layers were radially stretched in this example. In some embodiments, these multilayer precursor web materials were laminated in the finished web material.

In each embodiment, at least one piece of precursor web material of 67:33 -PGA: TMC manufactured according to example 1 was cut into circular pieces having an initial diameter of 15.24 cm. Embodiments using several layers of the precursor veil material were formed by placing several layers of the precursor veil material together before cutting. For each embodiment, the circular material was held in a clamping apparatus capable of stretching the precursor web material in all directions at an equal speed with a controlled temperature environment.

In each embodiment, eight equidistant clamps were placed around the periphery of the concrete precursor veil material approximately one centimeter (1) from the edge of the veil material. This effectively reduced the initial diameter of the precursor veil material from 15 cm to 12.7 cm. The attached precursor veil material was preheated to a temperature of 50 ° C for approximately two (2) minutes to raise the precursor veil material above the order-disorder temperature (Todt) of the particular polymer system used to make the material. of veil precursor. The softened precursor veil material was then stretched at a speed of 0.64 cm / second until the veil had a diameter of 30.48 cm. The four layer material was stretched to a final diameter of 35.56 cm at the same drawing speed. While holding in the stretched configuration, the stretched veil material was heated to 120 ° C for two (2) to three (3) minutes to heat set the stretched veil material.

The parameters of the layers, the weights of the area of the precursor web material and the drawing ratios (final diameter / initial diameter) of each article are listed in Table 11, below. The weight of the total area of the precursor web material is the product of the weight of the precursor layer area and the number of layers. For example, the weight of the macroscopic precursor area of Article 10-2 was approximately 90 mg / cm2 (2 layers x 45 mg / cm2). Article 10-6 occurred to a uniform aspect, but was not quantitatively analyzed. The weight of the area of the finished stretched veil is also listed in the table.

TABLE 11

Article ID

Layers Weight of the area of the precursor layer (mg / cm2) Stretching Ratio Weight of the stretched veil area (mg / cm2)

10-1

one Four. Five 2.8 3.68

10-2

2 Four. Five 2.4 9.43

10-3

2 22 2.8 5.87

10-4

2 10 2.8 2.75

10-5

4 10 2.8 5.40

10-6

6 Four. Five 2.4 Not measured

Figure 4A is a scanning electron micrograph (SEM) showing filaments of a radially drawn self-coherent web material of the present invention. The image, which represents radially oriented filaments in multiple directions after the drawing process, is of an alternative embodiment made with the 50% PGA copolymer: 50% TMC.

Example 11

This example provides a collection of the porosity values in various embodiments of the present invention. Initially, the precursor veil materials as described in example 1 were prepared at belt speeds of 7.9, 14.0, 20.4, and 48.0 cm / min, annealed with restraint and then the volume density and porosity percentage. Porosity percentage values were determined by controlling the height of the finished veil material with a glass microscope slide and an optical comparator as described in Example 8. The stretched veil materials of the present invention having the

E06788161

05-19-2015

Higher porosity percentage values were obtained with a belt speed of 48.0 cm / min.

Samples of the appropriate size of the precursor veil materials were stretched transversely as described in example 1 or biaxially stretched as described in example 8 or 9. The precursor veil material and various finished stretched veil materials were then evaluated. to determine the percentage of average porosity. The results of the percentage of porosity and the accompanying processing parameters are presented in Table 12. As seen in Table 11, the highest percentage of porosity possessed by the precursor web material was 89.7%. Consequently, all stretched self-coiled veil materials of the present invention have porosity percentage values of at least ninety percent (90%).

Table 12

Porosity of several precursor and stretched veil structures

BS

Belt speed (cm / min) Stretching Ratio Porosity percentage in the absence of additional components Manufacturing procedure (example number)

Transversal or Y axis

X axis

Precursor

48 na na 89.7 one

Biaxial

7.9 6: 1 3.6: 1 97.3 8

Biaxial

20.4 6: 1 3.6: 1 96.8 8

Biaxial-Fleece

7.9 6: 1 3.6: 1 98.1 9

Uniaxial

7.9 5: 1 89.8 one

Uniaxial

7.9 6: 1 90.7 one

Uniaxial

7.9 7: 1 91.8 one

Uniaxial

13 5: 1 92.5 one

Uniaxial

13 6: 1 92.7 one

Uniaxial

13 7: 1 90.9 one

Uniaxial

14 6: 1 94.0 one

Uniaxial

twenty 4: 1 90.7 one

Uniaxial

twenty 5: 1 92.2 one

Uniaxial

twenty 6: 1 93.2 one

Uniaxial

twenty 8: 1 94.4 one

Uniaxial

48 5: 1 94.6 one

10

As seen in Table 12, the porosity percentage increased for all embodiments of the stretched veil material of the present invention when compared to the precursor veil materials manufactured by the present inventors so that they have a percentage of porosity as high as possible with the technology currently available.

15 Example 12

This example describes the formation of an article of the present invention in a tubular form (Fig. 13).

In this example, a tubular article capable of stretching in a radial direction was formed using a combination of mandrel equipped with means for longitudinal extension of a wrapped sheath formed from a non-fixed precursor veil. The combination used is composed of a rigid roller or smaller tube ("mandrel") that can

20 be at least partially contained within the inside diameter of a circumferential means to fix the ends of the wrapped tube. At least one end of the tuno slides by manual or mechanical means along the axis of the mandrel to effect the desired longitudinal expansion ratio. As an alternative, once the tube has been formed and attached to the circumferential fixation, the mandrel can be removed and expansion is achieved through the tensile extension.

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

E06788161

05-19-2015

The articles were formed by wrapping a length of approximately 12.7 cm of an uncoated precursor web material (~ 9 mg / cm2) manufactured as described in example 1 around a metal mandrel of 0.953 cm in diameter and a portion of circumferential fixation sufficient to allow posterior physical attachment. The wrap was achieved by slightly overlapping the opposite edges to form a "cigarette type wrap." This step was repeated with offset seams to produce a multilayer tube (ie 2-10 layers (5 layers preferred) of the uncooked precursor veil material.

The union of the tube to the fixing means was achieved by fixing the overlapping ends of the tube against the circumferential edge with a copper wire. Then, the combination was placed in a preheated oven set at a temperature of 50 ° C for approximately two (2) minutes to soften the unbound polymeric material. The softened material was then stretched longitudinally at a ratio of approximately 5: 1. This was followed by fixing the sliding mandrel instead of heating the 100 ° C combination for five (5) minutes to fix (ie, anneal or completely crystallize) the final article.

This tubular form of the present invention showed a changeability from a first initial diameter to a larger second diameter when exposed to radial expansion forces. It was found that the tube formed in this example was easily distensible from a first diameter to a second diameter approximately twice as large as the first diameter.

Example 13

This example describes the formation of an article of the present invention in a tubular shape that has the ability to increase the diameter from a first initial diameter to a larger second diameter, combined with the ability to change the axial length (Fig. 17). .

As in the previous example, this article was formed by a multi-layered, non-annealed, multi-layered cigarette wrap around a 0.953 cm diameter metal mandrel and circumferential fixation. Then, the wrapped combination was placed in a preheated oven at a set temperature of 50 ° C for approximately two (2) minutes to soften the uncooked polymeric material. Then, the softened material was stretched longitudinally at a 5: 1 ratio, the slide fastener was immobilized and the combination was heated for 1 minute in an oven set at 100 ° C. The combination was removed and the opposite ends of the now stretched tubular form were urged towards each other to a length of approximately half of the original extension distance to compact the material along its length and in a manner similar to a accordion". The combination containing this "corrugated" tubular material was then heated at 130 ° C for five (5) minutes to impart a complete set to the final article. After completion and removal of the fixation article it was observed that the article retained the corrugated structure, which revealed the partial crystallization under the treatment conditions of 100 ° C.

In addition to having the easy ability to change the diameter when exposed to radial expansion forces, the article described in this example could also change in length. In addition, this article was more flexible and exhibited greater resistance to creasing when folded in a curved conformation than the article described in the previous example, cited above.

Example 14

This example describes the formation of an article of the present invention in a tubular form having at least one structural component incorporated in the article (Fig. 16).

A first completely fixed two-layer tubular shape was constructed as described in example 12, cut to a length of approximately 10 centimeters and then left on the mandrel without overlapping on the circumferential fixation. Then, a 0.051 cm diameter copper wire was wound helically around the outer surface of the tubular shape with spaces of approximately 0.635 cm between windings. A second tubular shape made of a precursor veil material of a width of approximately 12.7 cm intimately wrapped the first tubular form wound with wire and a portion of the circumferential fixation sufficient to allow its physical attachment. The combination was then wrapped with a superimposed surface polytetrafluoroethylene (ePTFE) tape-tube film. The longitudinal stretching of the tubular form was then performed as described above at a drawing ratio of 5: 1 to effect the simultaneous extension of the tube with a reduction in the internal diameter of the tubes. This process effectively compressed the outer tube in intimate contact with the underlying metal coil and the inner tube. This wrapped construction was then heated to 100 ° C for five (5) minutes to heat set the article. The surface PTFE film was removed from the finished article.

The article produced in this way was a metal coil enclosed within the superimposed and underlying layers of a PGA tube: self-cohesive nonwoven TMC stretched and flexible. This construct could serve as an implantable intravascular medical device, such as a stent or stent graft.

5

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

E06788161

05-19-2015

Example 15

This example describes the formation of a stretched self-coiled veil material of the present invention in the form of a flexible rope or roller (Fig. 14).

In this example, a stretched cord or self-cohesive filamentous form of flexible roller was formed by longitudinally stretching and axially rotating a length (2.54 cm wide X 25.4 cm long) of unstretched precursor veil material not annealed (9 mg / cm2) up to a point of tactile resistance. The length of the precursor material was extended approximately 15.25 cm and rotated approximately ten (10) times. Then, the material was stretched along its longitudinal axis at a stretch ratio greater than 2: 1. In this example, the precursor veil material was rotated and stretched by manual means, but mechanical procedures can also be used.

Then, the article was retained in its rotated form and heated in a furnace set at a temperature of 50 ° C for 1 minute, removed and then quickly stretched along its longitudinal axis to a distance twice that of its original length Then, the article was retained in its stretched form and then heated in a furnace set at 100 ° C for 5 minutes to heat set (ie annealing or complete crystallization) the final article.

The finished article appeared to be a highly flexible roller or rope that visually appeared to have a continuous pore structure through its cross section.

Example 16

This example describes the formation of a veil material of the present invention that has a very low volume density and a very high porosity percentage (Fig. 19).

Although a porous stretched veil material of any of the examples described above is suitable for use as a starting material for this material with a very high porosity percentage, a veil material manufactured according to example 1 was obtained at a drawing ratio. 6: 1 and an area density of 40 -50 mg / cm2 and was used as the starting veil material in this example.

The starting veil material was subjected to a carding procedure by placing the veil material on a granite surface plate, holding the veil material by hand and repeatedly eroding the filaments of the veil material in a random manner with a brush of wire. As the filaments of the veil material eroded, at least some of the veil filaments were hooked and separated by brush wires. As the filaments separated, the porosity percentage of the veil material increased and the volume density decreased. The visual appearance of the finished carded veil material was similar to that of a "cotton ball."

In another embodiment, at least one metal band is attached to the veil material (Figures 19A and 19B). Metal bands can serve as radiopaque markers to help visualize the veil material during and after implantation.

As described in example 17, this material has been shown to be thrombogenic and provides hemostasis in various circumstances. For example, the carded veil material of the present invention can stop, or significantly reduce, bleeding at the site of the incision in an important blood vessel, such as the femoral artery. Hemorrhage can also be stopped or significantly reduced in puncture wounds, lacerations or other traumatic injuries. The carded veil material described in this example can also be used to fill an aneurysm or occlude a blood vessel or other opening in the body of an implant recipient.

The highly porous veil material described herein can be combined with a release system (Figure 20), such as a catheter, to aid in the placement of the veil material in an indirectly accessible anatomical site.

This veil material can also be used as a component of an implantable medical device to help provide a liquid seal for the device against an anatomical structure or tissue.

Example 17

This example describes the use of a very highly porous veil material of the present invention to stop bleeding in an artery of an implant recipient.

Using a domestic pig model that had previously been heparinized, an eight French (8F) guide catheter was used to selectively access the cranial branch of the left renal artery. An angiogram was performed to obtain baseline images and the guide wire was removed. Then, a 6F guide catheter was introduced containing a combination of a piece approximately 7 mm in diameter by 20 mm in length of the veil material according to example 16 into the vasculature of the implant recipient across the length of the 8F catheter. The veil material of Example 16 contained a radiopaque marker band to help remotely visualize the present invention during and after implantation (Fig. 20).

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

E06788161

05-19-2015

Then, the marked veil material of example 16 was deployed in the cranial branch of the left renal artery mentioned above of the 6F catheter. After implantation of the marked veil material in the renal artery, partial occlusion of the blood vessel was observed, by angiogram, in thirty seconds. Complete occlusion of the blood vessel was observed three (3) minutes after deployment. It was interpreted that occlusion was due to blood clotting in the vessel at the implantation site, despite the presence of heparin.

A second procedure was performed on this implant recipient to demonstrate the ability of the veil material of example 16 to stop blood flow at a point of arterial incision. A femoral laceration was created with a partial femoral artery transaction. The artery occluded proximally, so there was only a retrograde flow. Despite this, bleeding at the incision site was profuse. Two pieces of the size of a cotton ball from Example 16 were then applied to the arteriotomy and kept under digital pressure for approximately 30 seconds. Although there was some blood leakage through the ball, the bleeding stopped completely in two minutes.

Example 18

For a model of a lesion of laceration of an organ, in this example pigs and canines were used with normal activated coagulation times (ACT) used for other vascular permeability studies. In order to induce a laceration in an organ, a puncture of 13 mm in diameter was performed in the liver or spleen of the implant recipient with a modified trephine. The puncture was allowed to bleed freely for forty-five

(45) seconds. Approximately 1 gram of the highly porous veil material described in Example 16 was applied by hand in the puncture with compression for one (1) minute. Then the pressure was released and the wound hemorrhage was evaluated. If the wound did not stop, pressure was reapplied for another minute and the evaluation was repeated.

For comparison, a commercially available chitosan-based hemostatic material (HEMCON; HemCon Inc., Portland, OR) was examined in the same organ laceration model. Both the highly porous web material described in example 16 and the HEMCON material successfully produced hemostasis after 1 minute of compression. The ease of handling and implantation of the present invention was considered superior to the HEMCON product.

Although the veil material of example 16 is in a "cotton ball-like" form, other forms of the highly porous veil material can be used for hemostasis and other medical circumstances that require thrombogenic results. These shapes include, among others, rollers or bundles of the veil material. The high compressibility of the present invention allows efficient packaging of the invention.

Example 19

This example demonstrates the thrombogenic properties of the present invention through the use of a comparative in vitro blood coagulation test that provides results expressed in terms of relative coagulation time (TCR).

To determine a coagulation time of whole blood in vitro for samples of different thrombogenic materials, approximately two (2) mg of each material of the test sample were obtained and placed individually in a microcentrifuge polypropylene tube. The sample materials used in this test were porous veil materials manufactured in accordance with Examples 1 and 16 and two commercially available hemostatic materials, HEMCON® Chitosan Patch (HemCon Inc., Portland, OR) and microporous polysaccharide beads with agent hemostatic HEMABLOCK® (Abbott Laboratories, Abbott Park, IL).

Figure 18 illustrates the steps taken for the relative coagulation time test. In the test, fresh non-heparinized arterial blood was collected from domestic pig and immediately mixed with sodium citrate to a final citrate concentration of 0.0105 M. One (1) ml of the fresh citrated blood was added to each sample tube. To facilitate the coagulation cascade, 100 µl of 1 M calcium chloride was added to each sample tube. The tubes were immediately capped and inverted 3 times. At each 30-second interval, the tubes were inverted for 1 second and returned to their vertical positions. The time was recorded when blood stopped flowing in a sample tube. Each test included a positive control (citrated blood + calcium only) and a negative control (citrated blood only). For each test, the clotting time was normalized to calcium control, with the smallest value indicating a global time to faster coagulation.

Veil materials manufactured according to example 1 and example 16 each reduced the relative coagulation time (TCR) to a value of approximately 0.7 when compared to the value of the positive control with citrated calcium of 1.0 . These materials also showed superior results to those of commercially available HEMCON hemostatic products, with an experimentally observed TCR of 1.0. With the powder of the hemostatic agent HEMABLOCK®, a TCR of 0.9 was observed.

5

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

E06788161

05-19-2015

Example 20

This example describes the formation of an article of the present invention to include a second bioabsorbable polymeric material (Fig. 9).

In this example, a finished 6: 1 veil material was obtained according to example 1 and was embedded with a film made of carboxymethyl cellulose (CMC). The CMC used was of high viscosity (1500-3000 cps at one percent (1%) at twenty-five degrees Celsius (25 ° C)) available in Sigma-Aldrich (St. Louis, MO, USA), catalog number C- 5013 A CMC film was formed from a gel concentration of 8 g of CMC / 100 ml of distilled water (8% w / v). The film had a thickness approximately equal to the thickness of the veil material to be embedded. The film was produced by rolling an 8% CMC gel bead on a flat metal plate and allowing the film to consolidate. The CMC gel film was then placed in contact with a piece of a similar size of veil material of Example 1 and tactile pressure was applied between two suitable release surfaces for approximately one (1) minute at room temperature. The veil material embedded in CMC was then dried under vacuum at 40 ° C, with occasional air purging.

This process was repeated with the CMC gel film placed on both sides of the veil material in a "sandwich" type relationship.

When wetted with saline, water or blood, the material described in this example generated a concentrated gel that showed significant adhesion that made the veil easily adaptable to the topography of many physical characteristics. It was recognized that such adhesion carried the potential to help a surgeon, interventional physician or other healthcare professional temporarily keep the present invention in a specific anatomical location, implantation site or near a surgical instrument or other implantable device. The CMC coating in dry or gel form may affect the permeation rate of various physiological fluids in or out of the underlying veil material.

Example 21

This example describes embedding carboxymethyl cellulose (CMC) in interstitial spaces of a 7: 1 veil material according to example 5, mentioned above. To manufacture this construction, high viscosity sodium carboxymethylcellulose ("CMC"; Sigma Chemical Company, St. Louis, MO) was dissolved in deionized water at a concentration of four percent (4%) (ie, 4 g / 100 ml) using an industrial mixer. The trapped air was removed by centrifugation. The CMC solution was embedded in the finished veil material (3.8 cm X 10.2 cm) using a roller to completely fill the porosity of the veil. The veil embedded in CMC was air dried at room temperature for sixteen hours (16 h) to produce a PGA veil material: self-cohesive TMC stretched embedded in CMC.

When wetted with saline, water or blood, the material described in this example generated a concentrated gel that showed significant adhesion that made the veil material easily adaptable to the topography of many physical characteristics. It was recognized that such adhesion carried the potential to help a surgeon, interventional physician or other healthcare professional temporarily keep the present invention in a specific anatomical location, implantation site or near a surgical instrument or other implantable device.

Example 22

This example describes embedding carboxymethyl cellulose (CMC) in interstitial spaces of a finished veil according to example 16 and dissolving the embedded CMC of the veil in phosphate buffered saline (PBS). To make this construction, 4% CMC was embedded in a sample of highly porous web material according to example 16 using a roller to completely fill in the empty spaces. The veil embedded in CMC was air dried at room temperature for sixteen hours (16 h) to produce a PGA veil material: self-cohesive TMC with high porosity embedded in CMC. The CMC embedded veil of Example 16 was then immersed in a PBS solution. After immersion, the CMC swelled to produce a PGA veil material: high-porosity self-cohesive TMC filled with hydrogel. After immersion for an additional ten (10) minutes, the CMC seemed to dissolve in the PBS and elute the veil material.

Example 23

This example describes embedding a carboxymethyl cellulose (CMC) in interstitial spaces of a veil material according to example 16. To make this construction, an eight percent CMC solution (8%) was embedded in a sample of veil material highly porous made in accordance with example 16 using a roller to completely fill the void spaces of the highly porous web material. The embedded veil was then dried under vacuum at 40 ° C to produce a PGA veil material: self-cohesive TMC with high porosity embedded in CMC. After immersion in PBS, the CMC swelled to produce a veil filled with hydrogel. After additional immersion for 10 minutes, the CMC dissolved and eluted from the veil material.

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

E06788161

05-19-2015

Example 24

This example describes embedding carboxymethyl cellulose (CMC) in the interstitial spaces of a veil material according to example 21 and crosslinking the CMC with itself within the veil material. To make this construction, a finished material was obtained in accordance with Example 21 and subjected to chemical crosslinking as taught in US Pat. No. 3,379,720, granted to Reid. In this process, the pH of the four percent CMC solution (4%) was adjusted to a pH 4 with the dropwise addition of thirty seven percent HCl (37%). Once the CMC was embedded and air dried according to Example 20, the compound was placed in an oven set at one hundred degrees Celsius (100 ° C) for one (1) hour to induce ester crosslinks between the carboxylic acid groups and the alcohol groups present in the chemical structure of CMC. The result was a PGA veil material: TMC stretched self-cohesive of high porosity on a crosslinked CMC material contained therein.

Example 25

This example describes the dilation of the crosslinked CMC veil material of example 24 in PBS. The material of example 24 was immersed in PBS for several minutes. After the dive, the CMC swelled to produce a veil filled with hydrogel. After additional immersion for two (2) days, the crosslinked chemical groups of the CMC material caused the CMC to be retained in the veil. Once filled with a crosslinker hydrogel, the veil material

or allowed the flow of PBS through it. The veil material of this embodiment effectively functioned as a fluid barrier.

Example 26

This example describes embedding polyvinyl alcohol (PVA) in the interstitial spaces of a 7: 1 veil finished according to Example 5. To make this construction, USP grade polyvinyl alcohol (PVA) was obtained from Spectrum Chemical Company, (Gardena, AC). The PVA was dissolved in deionized water at a concentration of ten percent (10%) (ie 10 g / 100 ml) using heat and stirring. The trapped air was removed by centrifugation. The PVA solution was embedded in a veil material (3.8 cm X 10.2 cm) according to example 5 using a roller to completely fill the empty spaces of the highly porous veil. The veil embedded in CMC was air dried at room temperature for sixteen hours (16 h) to produce a PGA veil material: self-cohesive TMC embedded in PVA.

Example 27

This example describes embedding polyvinyl alcohol (PVA) in interstitial spaces of a veil according to example 26 and dissolving the PVA of the veil in phosphate buffered saline (PBS). The PVA embedded web material of Example 26 was then immersed in a PBS solution. After immersion, the PVA swelled to produce a PGA veil material: self-cohesive TMC stretched full of hydrogel. After the dive for ten

(10) additional minutes, the PVA dissolved in the PBS and eluted from the veil material.

Example 28

This example describes the crosslinking of a material embedded in PVA according to example 26 with succinic acid. Once the PVA was embedded in a veil material according to example 26, the PVA was chemically crosslinked with succinic acid, a dicarboxylic acid, in accordance with the teachings of US Pat. No. 2,169,250, granted to Izard.

The PVA was dissolved in deionized water at a concentration of 10% (ie 10 g / 100 ml) using heat and stirring. Succinic acid (Sigma) was also dissolved in the PVA solution at a concentration of 2 g per 100 ml. The trapped air was removed by centrifugation. The PVA-succinic acid solution was embedded in a 7: 1 veil material (3.8 cm X 10.2 cm) according to example 5 using a roller to completely fill the empty spaces of the highly porous veil. The veil material was air dried at room temperature for sixteen hours (16 h). The compound was placed in an oven set at one hundred and forty degrees Celsius (140 ° C) for fifteen (15) minutes to induce ester crosslinks between the carboxylic acid groups present in the succinic acid and the alcohol groups present in the PVA.

Example 29

This example describes the crosslinking of a material embedded in PVA according to example 26 with citric acid. Once the PVA was embedded in a veil according to example 26, the PVA was chemically crosslinked with citric acid, a tricarboxylic acid, in accordance with the teachings of US Pat. No. 2,169,250, granted to Izard.

The PVA was dissolved in deionized water at a concentration of 10% (ie 10 g per 100 ml) using heat and stirring. Citric acid (Sigma) was also dissolved in the PVA solution at a concentration of 2 g per 100 ml. The trapped air was removed by centrifugation. The PVA-citric acid solution was embedded in a 7: 1 veil material (3.8 cm X 10.2 cm) according to example 5 using a roller to completely fill the empty spaces of the highly porous web material. The veil material was air dried at room temperature for

5

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

E06788161

05-19-2015

sixteen hours (16 h). The compound was placed in an oven set at one hundred and forty degrees Celsius (140 ° C) for fifteen (15) minutes to induce ester crosslinks between the carboxylic acid groups present in the citric acid and the alcohol groups present in the PVA.

Example 30

This example describes the crosslinking of a material embedded in PVA according to example 26 with aspartic acid. Once the PVA was embedded in a veil according to example 26, the PVA was chemically crosslinked with aspartic acid, a dicarboxylic amino acid.

The PVA was dissolved in deionized water at a concentration of 10% (ie 10 g / 100 ml) using heat and stirring. Aspartic acid (free acid, Sigma) was also dissolved in the PVA solution at a concentration of 1 g per 100 ml. The trapped air was removed by centrifugation. The PVA-aspartic acid solution was embedded in a 7: 1 veil material (3.8 cm X 10.2 cm) according to example 5 using a roller to completely fill the empty spaces of the highly porous web material. The veil material was air dried at room temperature for sixteen hours (16 h). The compound was placed in an oven set at one hundred and forty degrees Celsius (140 ° C) for fifteen (15) minutes to induce ester cross-links between the carboxylic acid groups present in aspartic acid and the alcohol groups present in the PVA.

Example 31

This example describes the crosslinking of a material embedded in PVA according to example 26 with carboxymethyl cellulose (CMC). Once the PVA was embedded in a veil according to example 26, the PVA was chemically crosslinked with CMC, a polycarboxylic acid.

The PVA was dissolved in deionized water at a concentration of 10% (ie 10 g / 100 ml) using heat and stirring. The CMC was also dissolved in the PVA solution at a concentration of 1 g per 100 ml. In this process, the pH of the one percent CMC solution (1%) was adjusted to pH 1.5 with the dropwise addition of thirty seven percent HCl (37%). The trapped air was removed by centrifugation. The PVA-CMC solution was embedded in a 7: 1 veil material (3.8 cm X 10.2 cm) according to example 5 using a roller to completely fill the empty spaces of the highly porous veil material. The veil material was air dried at room temperature for sixteen hours (16 h). The compound was placed in an oven set at one hundred and forty degrees Celsius (140 ° C) for fifteen (15) minutes to induce ester crosslinks between the carboxylic acid groups present in the CMC and the alcohol groups present in the PVA.

Example 32

This example describes the dilation of the hydrogel component of the constructs of Examples 28-31 in PBS. After immersing each of these constructions in a PBS solution, the PVA swelled to produce hydrogel-filled web materials of the present invention. After additional immersion for two (2) days, the PVA was intact within all the veil materials due to the presence of the chemical cross-links mentioned above. It was observed that each veil material filled with hydrogel prevented the movement of PBS through the veil material.

Example 33

This example describes embedding PLURONIC® surfactant in the interstitial spaces of a veil material according to example 5. The PLURONIC® surfactant is a copolymer of polyethylene glycol and polypropylene glycol available from BASF (Florham Park, NJ). Certain grades of the PLURONIC® surfactant form gels when immersed in hot biological fluids, such as grade F-127, as taught in US Pat. No. 5,366,735, granted to Henry. The PLURONIC® grade F-127 surfactant was dissolved in dichloromethane at a concentration of 5 g per 5 ml.

The solution of F-127 was embedded in a 7: 1 veil material (3.8 cm X 10.2 cm) according to Example 5 using a roller to completely fill the empty spaces of the highly porous veil material. The embedded veil material was dried at sixty degrees Celsius (60 ° C) for five (5) minutes. The embedded web material was immersed in PBS, preheated to 37 ° C. After immersion, the F-127 swelled to produce a veil material filled with hydrogel. After immersion for an additional day at 37 ° C, the F-127 dissolved and eluted from the veil material.

Example 34

This example describes the incorporation of a bioactive species into the hydrogel material of a veil material according to example 21 (Figure 9A). Dexamethasone (Sigma, St. Louis) was dissolved at a concentration of 10 mg / 100 ml in deionized water. Four grams of high viscosity CMC was added to the solution using an industrial mixer. The trapped air was removed by centrifugation. The CMC / dexamethasone solution was embedded in the finished veil using a roller and air dried at room temperature for 16 hours. After immersion in PBS, the CMC swells and it was observed that dexamethasone eluted from the hydrogel.

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

E06788161

05-19-2015

Example 35

This example describes the incorporation with physical crosslinking of a bioactive species into the hydrogel material of a veil material according to example 21. Dexamethasone phosphate (Sigma, St. Louis) was dissolved at a concentration of 10 mg / 100 ml in deionized water. Four grams of high viscosity CMC was added to the solution using an industrial mixer. The trapped air was removed by centrifugation. The CMC / dexamethasone phosphate solution was embedded in the finished veil using a roller and air dried at room temperature for 16 hours. After immersion in PBS, the CMC swells and it was observed that dexamethasone phosphate eluted from the hydrogel at a slower rate than in example 34, due to the formation of acid / base physical complexes between the basic dexamethasone phosphate and the Acid CMC

Example 36

This example describes the incorporation with chemical crosslinking of a bioactive species into the hydrogel material of a veil material according to example 24. Dexamethasone (Sigma, St. Louis) was dissolved at a concentration of 10 mg / 100 ml in water deionized Four grams of CMC was added to the solution using an industrial mixer. The pH of the dexamethasone / CMC solution was adjusted to pH 4 with the dropwise addition of thirty-seven percent HCl (37%). Once the dexamethasone / CMC solution was embedded and air dried according to Example 20, the compound was placed in an oven set at one hundred degrees Celsius (100 ° C) for one (1) hour to induce ester cross-links between the groups of carboxylic acid and the alcohol groups present in the chemical structure of CMC and among the carboxylic acid groups present in the CMC and alcohol groups present in dexamethasone. After immersion in PBS, the CMC swells and it was observed that dexamethasone eluted from the hydrogel at a slower rate than in Example 35, due to the formation of chemical ester bonds between dexamethasone and CMC.

Example 37

This example describes the incorporation with chemical crosslinking of a bioactive species into the hydrogel material of a veil material according to example 28. Dexamethasone (Sigma, St. Louis) was dissolved at a concentration of 10 mg / 100 ml in water deionized

The PVA was dissolved in the deionized water at a concentration of 10% (ie 10 g / 100 ml) using heat and stirring. Succinic acid (Sigma) was also dissolved in the PVA solution at a concentration of 2 g per 100 ml. The trapped air was removed by centrifugation. Next, the dexamethasone-PVA-succinic acid solution was embedded in a 7: 1 veil material (3.8 cm X 10.2 cm) according to example 5 using a roller to completely fill the void gaps. highly porous The veil material was air dried at room temperature for sixteen hours (16 h). The compound was placed in an oven set at one hundred and forty degrees Celsius (140 ° C) for fifteen (15) minutes to induce ester cross-links between the carboxylic acid groups present in the succinic acid and the alcohol groups present in the PVA and between the groups of carboxylic acid present in succinic acid and alcohol groups present in dexamethasone. Thus, dexamethasone was chemically bonded through ester bonds to succinic acid, which, in turn, chemically bonded through ester bonds to PVA. After immersion in PBS, the PVA swelled and it was observed that dexamethasone eluted from the hydrogel at a slow rate, due to the formation of ester bonds between dexamethasone and succinic acid / PVA.

Example 38

This example describes the formation of an article of the present invention to include an added material in combination with a stretched bioabsorbable veil. (Figure 12).

A series of holes (0.5 cm) were cut into two rectangular pieces of solvent molded film composed of the 85% d copolymer, l-PLA-co-15% PGA (available from Absorbable Polymers, Pelham, Alabama , USA). A rectangular piece of similar size of the finished 6: 1 veil material was obtained according to example 1 and placed between the two pieces of the film material and pressed at an elevated temperature and for a sufficient time to provide smoothness and penetration of the PLA: PGA copolymer in the interstices of the veil of Example 1. The resulting laminate compound possessed areas in which the enclosed veil material was exposed regionally through the holes in the film. Depending on the pressure applied, the temperature and the film used and the thickness of the veil, the porosity of the veil between the opposite film layers may or may not be filled. Alternatively, the film, with or without holes, can be applied to a single surface of the veil provided. When exposed to aqueous conditions at 37 ° C, the film component imparts a malleable stiffness that facilitates tactile manipulation of the veil construction and maintenance in a desired non-planar form before implantation.

The composition of the described laminated component or components may be selected from absorbable or non-absorbable synthetic or natural or synthetic materials with desirable properties that can additionally act as vehicles for bioactive agents and, alternatively, may act as a means that provides a controlled release rate. of the substance or bioactive substances contained. Laminated compound

5

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

E06788161

05-19-2015

described can alternatively be fixed by various available means to other absorbable or non-absorbable natural or synthetic materials to elicit a biological response (eg, hemostasis, inflammation), to provide mechanical support and / or as a vehicle for the release of bioactive agents.

Example 39

This example describes the construction of a composite material comprising a material of the present invention in combination with a compressing material (Figure 10). The material of the present invention helps to hold the compressing material instead of on a stapler during a surgical procedure (Figures 10A and 10B).

Two porous 6: 1 stretched self-wound veil materials obtained in accordance with Example 1 were obtained, cut into rectangular shapes of similar size with a laser following a laser following a pattern and stratified to form a bag between the layers. A laser that follows a pattern was also used to cut material that acts as a bioabsorbable compress with a rectangular shape made of a PGA block copolymer: TMC (67:33 weight percent) obtained from W.L. Gore & Associates, Inc., Flagstaff, AZ. The laser pattern controlled the exact dimensions of the three pieces of veil material. The laser pattern also provided four small alignment holes in the three pieces of veil material. Alignment holes were used to locate individual pieces on a mandrel and help weld the veil materials. The mandrel had a square transverse shape.

To construct the device, the two-layer piece of porous stretched veil material was wrapped around three of the four sides of the mandrel and held in place with location pins placed through laser cut holes. The compressing material was placed on the fourth side of the mandrel and held in place with location pins placed through the laser cut holes. Once the pieces had been properly juxtaposed, the combination was inserted over an ultrasonic welder and hot compression welds were formed along the two long edges of the rectangular veil materials to join the porous stretched veil material to the material What makes compress. The welds had a width of approximately 0.025 cm. The final form of the construction was generally tubular with a substantially square cross section. The ultrasonic welding was strong enough to hold the compressing material on the stapler during the handling of the compressing material, while remaining frangible enough to allow the compressing material and the sealing material. Porous stretched veil separates when a drag force is applied to the porous stretched veil material.

To help separate the compressing material from the porous stretched web material, a tensile polyethylene terephthalate (PET) cable was attached to the porous stretched web material before the aforementioned ultrasonic welding process. A tongue was provided to the free end of the traction cable. After the construction of the composite material, the attached traction cable was rolled up and stored in the bag with the tongue exposed.

In a similar embodiment, perforations were made in the compressing material adjacent to the ultrasonic welds to help separate the compressing material from the porous stretched web material.

Example 40

This example describes the construction of a composite material comprising a material of the present invention in combination with a non-bioabsorbable material (Figure 15). In this embodiment, the bioabsorbable material occupies a different area from that of the non-bioabsorbable material of the compound. In particular, this composite material of the present invention is useful as an implantable dental device in which the non-bioabsorbable portion of the device can remain in the body of an implant recipient, while the bioabsorbable portion disappears from the body of the implant recipient in a predictable time period. In this embodiment, a second implantable dental device may be placed in the area of the present invention originally occupied by the bioabsorbable portion of the invention.

A finished 6: 1 veil material was obtained according to Example 1 and cut into an oval shape of a width of approximately 0.5 cm X 0.75 cm in length. A rectangular piece of porous expanded polytetrafluoroethylene (ePTFE) of medical grade with rounded corners was obtained from W.L. Gore & Associates, Inc., Flagstaff, AZ. The ePTFE material had a width of 0.75 cm and a length of 1.0 cm. A hole in the ePTFE was cut slightly smaller than the external dimensions of the material of example 1. The material of example 1 was placed over the hole and the solvent was bonded in place using a small amount of a PLA solution: TMC / Acetone applied along the edge of the hole sufficient to dissolve and flow some of the material from Example 1 into the porous structure of the ePTFE material. The acetone solution used was composed of approximately 20% (w / v) poly (70% lactide-co-30% trimethylene carbonate), or commercially available copolymer at Boehringer Ingelheim, (Ingelheim, Germany and Petersburg, Virginia, USA) The composite material was briefly placed in a heated oven below the melting point of the material of the

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

E06788161

05-19-2015

Example 1 and under reduced pressure to completely remove the acetone solvent from the implantable medical device.

The device of this example is particularly suitable for medical situations that require regrowth, or regeneration, of tissue at the site of the defect or injury. For example, in some dental applications a space is created or enlarged in the jaw as part of a repair procedure. Unless the surrounding gingival tissue is prevented from filling the space, the bone will not grow back in the space as desired. The device of this example is placed on the space in the bone to prevent the growth into unwanted tissues in the space, while the growth of the desired bone tissue is encouraged. With conventional devices manufactured from ePTFE alone, the ePTFE remains permanently at the implantation site. In some situations, it may be desirable to place a second implantable dental device, such as a metal bracket, in the newly grown bone tissue. Providing an ePTFE tissue barrier material with a bioabsorbable material according to the present invention would allow the bioabsorbable portion of the device to disappear from the implantation site and leave an unobstructed path through the ePTFE material to place a second dental implant.

Example 41

This example describes the construction of a composite material of the present invention having a non-bioabsorbable component combined with a bioabsorbable component (Figure 21). In this example, a 6: 1 bioabsorbable veil material finished as described in example 1 joins a porous expanded polytetrafluoroethylene material to form an implantable sheet. The sheet can be used as a replacement, or substitute, for various anatomical membranes. In particular, these membranes are useful as substitutes for dura and other nervous system membranes.

A bioabsorbable material was obtained according to example 1 and enzyme was placed from a thin ePTFE sheet material having fragile fibrils and spacious pore volumes. The ePTFE material was manufactured in accordance with US Pat. No. 5,476,589 granted to Bacino.

The two sheets of material were bound with solvent using the PLA: TMC / acetone solution described above. Once bound, the acetone was removed with heat and vacuum. The result was a composite sheet material suitable for use as an implantable medical device.

Example 42

This example describes the use of a porous self-cohesive stretched veil material of the present invention as an external support wrapper for an anatomical structure or organ (Figure 11). The wrap can also be used in an anastomotic site to minimize tissue loss and adhesions.

In this example, a study of tissue compatibility was performed in a group of animals. In the study, a piece of porous self-cohesive stretched veil material manufactured according to example 1 was cut into a rectangular piece of 2 cm X 5 cm. The uniaxially finished 6: 1 stretched veil material of Example 1 exhibited ability to lengthen in the longest dimension of the veil (i.e., 10 cm). A control material made of non-bioabsorbable materials was obtained from W.L. Gore & Associates, Inc., Flagstaff, AZ under the trade name PRECLUDE® Dura Substitute (PDS).

For the assays, two sites in the colon of each of eight (8) New Zealand White rabbits were used. At a distal site approximately 5 cm from the anus, a piece of one of the test materials was wrapped around the colon. Five centimeters above the colon, more proximal, another piece of test material, different from the first piece, was wrapped. The materials formed covers around the serosa of the colon and were glued in place with GORE-TEX® Sutures.

At the end of seven (7) days and thirty (30) days, all animals were sacrificed and the various materials recovered intact. The particular segment of the colon wrapped with any accompanying adhesion was immersed in 10% neutral buffered formalin for paraffin histology. The adhesions to the materials were scored.

After macroscopic evaluation and histological analysis of the veil material of the present invention, incorporation of the veil material in the serosa was shown at seven (7) days. The veil material of the present invention was incorporated well into the serosa of the colon, as well as the surrounding adhesions on the thirty-first day (31). It was seen that the veil material of the present invention was highly vascularized at seven (7) and thirty-one (31) days. The PDS was not incorporated into the serosa at seven (7) and thirty-one (31) days, nor was the material vascularized.

The use of a veil material of the present invention in combination with a coating of a bioabsorbable adhesion barrier material, such as a partially crosslinked polyvinyl alcohol (PVA) biomaterial, carboxymethylcellulose or hyaluronic acid could be advantageous.

5

10

fifteen

twenty

25

30

35

40

Four. Five

fifty

55

60

E06788161

05-19-2015

Example 43

This example describes the construction of an embodiment of the present invention in the form of a compound that has sufficient thrombogenic properties to quickly stop bleeding and provide hemostasis at the site of bleeding.

A highly highly porous stretched self-coiled web material of the present invention was constructed as described in example 16, cited above, and has been shown to have thrombogenic properties similar to those described in example 18, cited above.

Referring to Figures 21-21E, the veil material (22) adhered to a substrate material (24, 29) to form a compound (21). In this example, the stable substrate material in the form of a porous foamy polytetrafluoroethylene (PTFE) material having a layer of high strength tetrafluoroethylene barrier material placed between the veil material and the PTFE material to prevent permanent adhesion of the Veil material to the porous PTFE material prevent inward cell growth or cellular processes in the porous PTFE material.

The foamy PTFE material was made in accordance with the teachings of US Pat. No. 5,429,869, granted to McGregor et al. The foamable PTFE substrate material was made by combining a dispersion of PTFE particles with a population of expandable thermoplastic microspheres. After exposure to heat or another energy source, the gas contained in the microspheres expanded. As the microspheres expanded, the surrounding PTFE material shifted and formed a three-dimensional framework structure, or network, made of coherent expanded PTFE nodes and fibrils and expanded microspheres. The interaction of PTFE and microspheres caused PTFE to expand in three dimensions. The resulting foamy PTFE product had, among others, a uniform distribution of nodes and fibrils in all directions, flexibility and a degree of resilient compressibility. Such thermoplastic microspheres are commercially available from Nobel Industries Sweden, Sundsvall, Sweden, under the name EXPANCEL® commercial. These microspheres can be obtained in various sizes and shapes with expansion temperatures that generally vary from 80 ° C to 130 ° C. A typical EXPANCEL® microsphere has an initial average diameter of 9 to 17 micrometers and an expanded average diameter of 40 to 60 micrometers. According to Nobel Industries, the microspheres have a true unexpanded density of 1250-1300 kg / m3 and an expanded density of less than 20 kg / m3. A mixture of PTFE, in the form of paste, dispersion or powder, and microspheres, in the form of dry powder or solution, is mixed in proportions of 1 to 90% by weight of microspheres, with 5 to 85% by weight of microspheres being preferred. It should be appreciated that a wide range of products can be created, even with a percentage of microspheres of simply 0.1 to 5% by weight; similarly, for some uses, filled products with a percentage of microspheres of and / or other charges between 90 to 909 or more by weight can be created. The mixing can be produced by any suitable means, including dry powder mixing, wet mixing, coagulation of aqueous dispersions and suspended loads, high shear mixing etc. After mixing, preferably the resulting composition is heated to a temperature of 80 ° C to 170 ° C for a period of 0.5 to 10 minutes to activate the microspheres. No sintering of the resulting porous foam PTFE material was performed. The foamy PTFE material used in this example was obtained in W.L. Gore & Associates, Inc. (Elkton, MD, catalog number 7811156).

A sheet of a fluoropolymeric material, having a density greater than 2.0 g / cm 3, was laminated in the foamed PTFE material to serve as a carrier material for the bioabsorbable web material. The carrier material can also serve as a barrier material to liquids and / or inward cell growth or cellular processes. The sheet of fluoropolymeric material was in the form of a single layer of a thin polytetrafluoroethylene (PTFE) membrane having a thickness of approximately 0.005 mm. The membrane had a tensile strength of approximately 49,000 psi (approximately 340 KPa) in a first direction and a tensile strength of approximately 17,000 psi (approximately 120 KPa) in a second direction perpendicular to the first direction. Tensile measurements were made at 200 mm / min. The loading rate with a mandibular space of 2.5 cm. The finished membrane had a density of approximately 2.14 g / cm. The PTFE membrane was bonded to the foamed PTFE material with heat and pressure applied with a manual welder (Weber Model No. EC2002-M, available from McMaster Carr). The temperature of the welders was set at 427 ° C.

The very highly porous stretched self-absorbed bioabsorbable web material adhered to the PTFE membrane carrier material with a bioabsorbable copolymer composition of polylactic acid and polyglycolic acid dissolved in an acetone solvent. This solution of bioabsorbable adhesive material was applied to the exposed surface of the thin PTFE membrane carrier material, followed immediately by the placement of the veil material on the adhesive material so that a population of filaments of the veil material in contact with the adhesive solution . When the acetone solvent had evaporated from the adhesive material, the population of filaments in contact with the adhesive was attached to the thin PTFE membrane material portion of the substrate material. A scheme of this construction is illustrated in Figure 22.

The finished construction is placed inside a metal foil storage bag and sterilized by exposure to ethylene oxide. The storage bag is provided with a material from the triboelectric series to generate a static electricity charge on the construction, in particular the material

E06788161

05-19-2015

of veil, as the construction is removed from the storage bag.

Example 44

This example describes the use of the present invention to establish hemostasis at a bleeding site in a subject homeothermic animal. An embodiment of the present invention as described in example 43, cited above, was obtained and placed on a traumatized pig liver suffering from severe bleeding. The bioabsorbable veil material of the invention was placed on the hemorrhagic tissue and manual pressure was applied to the non-bioabsorbable portion of the invention to keep the veil material in contact with the hemorrhagic tissue. After several minutes (for example, less than ten minutes), the pressure applied manually was relieved and it was observed that the bleeding had stopped. After hemostasis, the non-bioabsorbable component of the invention was left in the

10 place of bleeding for a while to allow a short warm-up period and the subsequent incorporation of the bioabsorbable veil material. Once a degree of healing has occurred, the non-bioabsorbable component was easily and nontraumably removed from the bioabsorbable veil material and removed from the subject animal's body.

Claims (19)

5 10 fifteen twenty 25 30 35 40 Four. Five fifty

one.

An implantable article comprising continuous bioabsorbable filaments formed by fusion and discontinuous bioabsorbable filaments formed by fusion intermingled to form a porous veil (22), wherein said filaments are self-coherent with each other at multiple points of contact, wherein said filaments comprise at least one semicrystalline polymer component covalently bonded or mixed with at least one amorphous polymer component, in which the filaments possess partial to complete immiscibility of the phases of the polymer components when in a crystalline state; and wherein said porous veil has a percentage of porosity greater than ninety in the absence of additional components, in which the porous veil is a uniaxially stretched veil and in which the filaments have been eroded through a carding procedure when the minus some of the filaments of the veil are hooked and separated from each other; and a non-bioabsorbable material (24) removably attached to a population of said filaments formed in fusion.

2.

 The implantable article of claim 1, wherein the percentage of porosity is greater than ninety-one.

3.

 The implantable article of claim 1, wherein the at least one semicrystalline polymer component is covalently bonded to at least one amorphous polymer component.

Four.

 The implantable article of claim 1, wherein the at least one semicrystalline polymer component is mixed with the at least one amorphous polymer component.

5.

 The implantable article of claim 3 or claim 4, wherein at least one of the components is a block copolymer.

6.

 The implantable article of claim 1, wherein at least one semicrystalline polymer component has a melting point greater than eighty degrees Celsius (80 ° C).

7.

The implantable article of claim 1, further comprising a bioabsorbable material bonded to a population of said filaments formed by fusion.

8.

The implantable article of claim 7, wherein the bioabsorbable material is in the form of continuous filaments formed by fusion intermingled to form a porous veil, wherein said filaments are self-coherent with each other at multiple points of contact, wherein said filaments they comprise at least one semicrystalline polymer component covalently bonded or mixed with at least one amorphous polymer component, in which the filaments possess partial to complete immiscibility of the phases of the polymer components when in a crystalline state.

9.

The implantable article of claim 1 in the form of a substantially flat sheet.

10.

 The implantable article of claim 1 in the form of two or more flat sheets.

eleven.

The implantable article of claim 10, wherein said sheets are joined together to form a laminate.

12.

 The implantable article of claim 1, 10 or 11, wherein the non-bioabsorbable material is in the form of a sheet.

13.

The implantable article of claim 12, wherein said non-bioabsorbable sheet comprises a fluoropolymeric material.

14.

 The implantable article of claim 13, wherein said fluoropolymeric material is polytetrafluoroethylene.

fifteen.

 The implantable article of claim 12, when dependent on claim 1 or claim 11, wherein said non-bioabsorbable sheet material has a side that is a barrier to inward cell growth.

16.

 The implantable article of claim 12, when dependent on claim 11, wherein said non-bioabsorbable sheet material has a second side that is a barrier to inward cell growth.

17.

 The implantable article of claim 15, wherein said population of filaments is attached to said side of said non-bioabsorbable sheet material that is a barrier to inward cell growth.

18.

The implantable article of claim 17, wherein said population of filaments is attached to said second side of said non-bioabsorbable sheet material that is a barrier to inward cell growth.

19.

A method of manufacturing an implantable article according to claim 1, the process comprising:

3. 4 providing a porous precursor web material comprising intermingled continuous bioabsorbable filaments formed by fusion and discontinuous bioabsorbable filaments formed by fusion, wherein said filaments are self-coherent with each other at multiple points of contact, wherein said filaments comprise at least one polymer component semicrystalline covalently bound or mixed with at least 5 an amorphous polymer component, in which the filaments have partial to complete immiscibility of the phases of the polymer components when in the crystalline state; stretching said precursor veil material in a uniaxial direction; annealing said stretched precursor veil material; erode the filaments of the veil material through a carding procedure so that at least 10 some of the filaments of the veil get caught and separate from each other; and removably joining a non-bioabsorbable material to the veil material. 35